Refined ecclesiasticism, resulting in the tension which subsequently relieved itself in the general destructiveness of the Thirty Years' War, made the sojourn of Jews, both in Catholic and Protestant countries, a continual torture. Luther's followers in Germany forgot what Luther had so earnestly uttered in their favor, only remembering the hateful things of which, in his bitterness, he had accused them. The Jews of Berlin and the province of Brandenburg, for instance, had the sad alternative put before them of being baptized or expelled. A Jewish financier, the physician Lippold, favorite of Elector Joachim II, and his right hand in his corrupt, financial schemes, examined and tortured on the rack by Joachim's successor, John George, admitted, though afterwards recanting, that he had poisoned his benefactor. The Jews were driven also out of Brunswick by Duke Henry Julius. Catholic nations and princes had no cause to reproach their Protestant opponents with toleration or humanity in regard to Jews.

It was, in some respects, fortunate for the Jews of Germany and Austria, that the reigning emperor, Rudolph II, although a pupil of the Jesuits, educated in a country where the fires of the stake were always smoking, and a deadly enemy of the Protestants, was not greatly prejudiced against Jews. Weak and vacillating, he was not able to check the persecutions directed against them, but at least he did not encourage them. He issued an edict to one bishop (of Würzburg) that the Jews should not be deprived of their privileges, and to another (of Passau) that they should not be tortured on the rack. But, in order not to be decried by his contemporaries or by posterity as a benefactor of Jews, he not only maintained the heavy taxation of Jews in his crown land, Bohemia, but from time to time increased it. He also ordered the Jews to be expelled from the archduchy of Austria within six months.

In this position, robbed by Catholics and Lutherans alike, trampled down or driven into misery, barely protected by the emperor, but taxed under the pretense of enjoying this protection, the ruin and degradation of German Jews reached ever lower depths. They were so sorely troubled by the cares of the moment, that they neglected the study of the Talmud, once their spiritual food.

The Jews of Italy fared even worse at this time, and they, too, sank into misery and decay. Italy was the principal seat of the malicious and inexorable, ecclesiastical reaction, animated with the thought to annihilate the opponents of Catholicism from the face of the earth. The torch of civil war was hurled from the Vatican into Germany, France, and the Netherlands. And as the Jews, from the time of Paul IV and Pius V, had been upon the list of heretics, or foes of the church, their lot was not to be envied. With the loss of their independence, their numbers also decreased. There were no Jews living in southern Italy. In northern Italy, the largest communities, those of Venice and Rome, numbered only between 1,000 and 2,000 souls; the community in Mantua had only 1,844; and in the whole of the district of Cremona, Lodi, Pavia, Alessandria, and Casalmaggiore, there dwelt only 889 Jews. Pius V, by nature a sinister ecclesiastic delighting in persecution, who treated Jews as the cursed children of Ham, was succeeded by Gregory XIII (1572–1585), who had been skillfully trained to fanaticism by the Jesuits and the Theatine monks. As regards Jews, Gregory was a most consistent follower of the cruelty of his predecessor. In spite of repeated warnings, there were still many Christians in Italy, who, in their blindness, preferred Jewish physicians of proved excellence, such as David de Pomis, or Elias Montalto, to Christian charlatans. Gregory was desirous of prohibiting their employment. He renewed the old canonical law that Christian patients were not to be treated by Jewish physicians; not only visiting Christians who transgressed this command with severe penalties, but also punishing the Jewish physicians if they ventured to prolong the life of a Christian patient, or even alleviate his sufferings. His severity succeeded. Another of Gregory's edicts referred not to one profession, but to the Jewish race in general. He placed them under the Argus eye of the Inquisition. If any of them maintained or taught what was heretical, i.e., obnoxious to the church; if he held intercourse with a heretic or an apostate, helped him or showed him sympathy, he was to be summoned by the Inquisition, and according to its verdict was to be condemned to confiscation of his property, the punishment of the galleys, or even sentenced to death. If, then, a refugee Marrano from Spain or Portugal was caught in Italy, and it was proved that a brother Jew had given him food or shelter, both might expect to be seized by the inexorable arm of the Inquisition of Italy. The anger of Pope Gregory XIII was poured forth also against the Talmud. The Jews were once more admonished to deliver up the Talmud and other works suspected of being hostile to the church. The Inquisitors and other spiritual authorities were appointed to institute search for these books everywhere. Anyone subsequently found in possession of them, even after declaring that the offending passages had been expunged, was rendered liable to severe punishment. Pope Gregory XIII's most zealous effort was directed to the conversion of Jews. This pope, who most heartily encouraged the Jesuits and their proselytizing school of thought, endowed a propagandist seminary of all nations—the curriculum included twenty-five languages—called the "Collegium Germanicum," issued a decree that on Sabbaths and holy days Christian preachers should deliver discourses upon Christian doctrine in the synagogues, if possible in Hebrew, and that Jews of both sexes, over twelve years of age, at least a third of the community, must attend these sermons. The Catholic princes were exhorted to support this vigorous attempt at conversion. Thus an ordinance of a half-mad, schismatic pope, Benedict XIII, issued in a moment of passionate excitement, was sanctioned, and even exaggerated in cold blood by the head of the united Catholic church, thereby exercising religious compulsion not very different from the act of Antiochus Epiphanes in dedicating the Temple of the one true God to Jupiter. It is characteristic of the views then prevailing, that the Jews were to provide salaries for the preachers, in return for the violence done their consciences! Like his predecessor, Pius V, Gregory spared no means to win over the Jews. Many allowed themselves to be converted either from fear or for their advantage; for Gregory's edicts did not remain a dead letter, but were carried out with all strictness and severity. The consequence was that many Jews left Rome.

The condition of the Jews in Rome was apparently altered under Gregory's successor, Sixtus V (1585–1590), who rose from the position of a swine-herd to the office of the shepherd of Catholic Christendom, and whose dauntless energy in the government of the Papal States stamped him as an original type of character. He allowed Jews to be around him, and harbored Lopez, a Jewish refugee from Portugal, who made various suggestions as to the improvement of the finances. He went still further; he issued a bull (October 22d, 1586), which did away with almost all the restrictions made by his predecessors. Sixtus not merely granted Jews permission to dwell in all the cities of the Papal States, but also allowed them to have intercourse with Christians and employ them as assistants in business. He protected their religious freedom by special provisions, and extended to them an amnesty for past offenses, i.e., for condemnations on account of the possession of religious books. Moreover, he forbade the Knights of Malta to make slaves of Jews traveling by sea from Europe to the Levant, or vice versâ, a practice to which these consecrated champions of God had hitherto been addicted. Pope Sixtus knew how to secure obedience to his command when it became law, and the Jews previously expelled now returned to the papal dominions. Under him the Jewish community at Rome numbered two hundred members. Finally he removed the prohibition which prevented Jewish physicians from attending Christian patients. The compulsory services instituted by his predecessor were the only ordinances that Sixtus V allowed to remain.

The permission, so important at that time, for Jewish physicians to have access to Christian patients, was probably gained for himself and his colleagues, by the then celebrated physician, David de Pomis (born 1525, died 1588). With medical knowledge he combined linguistic acquirements, and familiarity with Hebrew and classical literature, writing both Hebrew and Latin with elegance. In the course of his life he felt keenly the changes in the papal policy. He lost all his property through the hostile decrees of Paul IV, was kindly treated by Pius IV, and allowed by way of exception to practice among Christians in consequence of a splendid Latin discourse delivered before the pope and the college of cardinals. But he was again subjected to irritating restrictions by Pius V, and had to employ his skill in the service of petty, capricious nobles. To dispel the unconquerable prejudices against Jews, particularly against Jewish physicians, De Pomis wrote a Latin work, entitled "The Hebrew Physician," which affords favorable testimony to his noble mind and extensive culture. With considerable eloquence De Pomis maintained that the Jew was bound by his religion to love the Christian as his brother, and that a Jewish physician, far from wishing to do harm to his Christian patient, was wont to treat him with the utmost care and solicitude. He enumerated various Hebrew physicians who had attended princes of the church, cardinals and popes, had restored them to health, and had received distinctions from them and from cities. In conclusion, De Pomis adduced some proverbs from the Talmud in a Latin translation, to show that this much-calumniated book was not so harmful and corrupt as enemies of the Jews asserted. This apology for Judaism and Jewish physicians, dedicated to Prince Francesco Maria of Urbino, the elegant Latin style of which was highly praised by an experienced critic of the time, appears to have made an impression upon Pope Sixtus. De Pomis must certainly have been intimate with him, as he was allowed to dedicate to him his second important literary work, a dictionary of the Talmud in three languages.

The pope severely punished a Christian Shylock, because he claimed a pound of flesh from a Roman Jew as the result of a wager. This Christian, named Seche, had wagered with a Jew, named Ceneda, that St. Domingo would be conquered, and on winning his bet he claimed the penalty. On hearing of this, Sixtus condemned him to death, but afterwards mitigated the punishment to banishment, and allotted the same fate to Ceneda for wagering his body, the property of his sovereign.

The favorable attitude of Sixtus towards Jews encouraged them in the hope—to them a matter of conscience, of life itself—that the prohibition directed against the Talmud and the Hebrew Scriptures would be removed forever. Under the last two popes no copies of the Talmud had been allowed to appear without causing the possessor to incur the dangers of the watchful Inquisition. Nor was the possession of other perfectly harmless Hebrew works without risk, for as the Inquisitors and clerical authorities did not in the least understand them, they condemned all without exception as inimical to the church, a category which afforded ample room for denunciation. Whether the possessor of a Hebrew book should be condemned to lose his property, or be sent to the galleys, depended, in the last instance, upon the decision of baptized Jews acquainted with rabbinical literature. To escape these annoyances the communities of Mantua, Ferrara, and Milan addressed a request to Sixtus V to allow the Jews to possess copies of the Talmud and other books, provided these works were previously expurgated of the passages objectionable to Christianity. They referred to the decision of Pope Pius IV that the Talmud could not be entirely condemned, but that it contained passages worthy of censure, which were to be struck out by the censor's marks. A Jewish delegate, Bezalel Masserano, had gone to Rome, provided with 2,000 scudi, in order to lay the request of the Jews at the feet of his Holiness. It was granted in the bull of October 22d, 1586. Sixtus allowed the reprinting of the Talmud and other writings, though only after censorship. For this purpose two commissions were appointed, in which baptized Jews were naturally included as experts. The Italian Jews began to rejoice at being allowed to possess even a mutilated Talmud. But scarcely had the commission arranged the conditions of the censorship (August 7th, 1590), when the wise pope died, and the undertaking, just begun, of reprinting the mutilated Talmud was at once discontinued.

The regard paid Jews by Sixtus V arose not from any sentiment of justice, but from his passionate desire to amass treasure. "This pope bled Christians from the throat," says his biographer, "but he drew the blood of Jews from all their limbs." They often found themselves compelled to pay immense sums into the papal treasury.

With Clement VIII, however (1592–1605), the system of intolerance, practiced by Paul IV, Pius V, and Gregory XIII, once more came into vogue. He repeated the edict of expulsion against the Jews in the Papal States (February 25th, 1593), and allowed them to dwell only in Rome, Ancona, and Avignon. If a Jew were caught in any other papal city, he was to expiate his offense by the loss of his property and the penalty of the galleys. Clement re-imposed the old restrictions upon the Jews in the three cities mentioned, forbidding them either to read or possess the Talmud and other rabbinical writings. The Jews, expelled from the Papal States, seem to have been received by Ferdinand, Duke of Tuscany, who assigned Pisa to them as a dwelling-place (July, 1593). He allowed them to possess books of every kind and of all languages, including the Talmud, but the copies first had to be expurgated according to the regulations of the commission instituted by Sixtus V. So great was the fanaticism of the apostolic throne that even noble princes, like Ferdinand de Medici, of Tuscany, and Vicenzo Gonzago, of Mantua, did not venture to relax it. Even in places where, as a favor, the Jews were allowed to possess expurgated books, they were exposed to all kinds of annoyances and extortions. They had to pay the censors, mostly baptized Jews, for the mutilation of these writings, nor were they assured that even then their books would not again be confiscated, and the owners punished, merely because some obnoxious word or other had remained unobliterated. Woe to those who rubbed out one of the censors' marks! To avoid being exposed to vexation, Jews themselves laid hands upon their sacred literature, and expunged not only everything that referred to idolatry, but also everything that glorified the Jewish race, or made mention of the Messiah and his future advent. As Italy, at that time, was the chief market for printed Hebrew works, the Jews in other countries received only mutilated copies, from which open or covert protests against Rome were completely obliterated.