Leo Modena was more in earnest with the attack on the Kabbala, which had become burdensome and repulsive to him. He felt impelled to discharge destructive arrows against it, and this he did with masterly skill. He called the anti-Kabbalistic work, which he dedicated to his disciple Joseph Chamiz, a Luryan enthusiast, "The Roaring Lion" (Ari Noham). From many sides he threw light on the deceptions, the absurdity, and the falsehood of the Kabbala and its fundamental source, the Zohar. Neither this work nor his attacks on Talmudical Judaism were published by him: the author was not anxious to labor in either direction. To a late age he continued his irregular life, without striving after real improvement. Leo Modena died, weary of the conflict, not with gods (i. e., ideas) and men, but with himself, and of the troubles which he had brought upon himself.

Apparently similar, yet differing fundamentally from him, was the third burrower of this period: Joseph Solomon Delmedigo (born 1591, died 1655). Scion of an old and noble family, in whose midst science and the Talmud were cultivated, and great-grandson on the female side of the clear thinker Elias del Medigo, he but slightly resembled the other members of his house. His father, a rabbi in Candia, had not only initiated him into Talmudic literature, but also made him learn Greek. Later Delmedigo acquired the literary languages of the time, Italian and Spanish in addition to Latin. The knowledge of languages, however, was only a means to an end. At the University of Padua he obtained his scientific education; he showed decided inclination for mathematics and astronomy, and could boast of having as his tutor the great Galileo, the discoverer of the laws of the heavens, the martyr to natural science. By him he was made acquainted with the Copernican system of the sun and the planets. Neither Delmedigo nor any believing Jew labored under the delusion that the stability of the sun and the motion of the earth were in contradiction to the Bible, and therefore heretical. Delmedigo also studied medicine, but only as a profession; his favorite subject continued to be mathematics. He enriched his mind with all the treasures of knowledge, more varied even than that of Leo Modena, to whom during his residence in Italy he clung as a disciple to his master. In the circle of Jewish-Italian semi-freethinkers he lost the simple faith which he had brought from home, and doubts as to the truth of tradition stole upon him, but he was not sufficiently animated by a desire for truth either to overcome these doubts and become settled in the early belief to which he had been brought up, or unsparingly to expose the false elements in Jewish tradition. Joseph Delmedigo was as little formed to be a martyr to his convictions as Leo Modena, the latter by reason of fickleness, the former, of insincerity.

With doubt in his heart he returned to his home in Candia, and gave offense by his free mode of thought, especially by his preference for secular knowledge. He made enemies, who are said to have persecuted him, and was obliged to leave his native land. Then began a migratory life, which drove him from city to city, like his model Ibn-Ezra. Like him, he made friends with the Karaites wherever he met them, and they thronged to his presence. At Cairo Delmedigo celebrated a complete triumph with his mathematical knowledge, when an old Mahometan teacher of mathematics, Ali Ibn-Rahmadan, challenged him, a youth, to a public combat, in which Ali was beaten. The victorious combatant was magnanimous enough to show honor to Ali before the world. Instead of betaking himself to Palestine as he had intended, Delmedigo traveled to Constantinople; here also he attached himself to the circle of the Karaites, and at last passed through Wallachia and Moldavia to Poland. There, mathematics procuring him no bread, he practiced medicine, of which, however, he had learnt more from books than by the bedside of patients. In Poland he passed for a great physician, and was taken into the service of Prince Radziwill, in Wilna (about 1619–1620). Here, through the excessive attention given to the Talmud, general culture was forsaken, but youths and men eager for learning, especially Karaites, thronged to Delmedigo to slake their thirst for knowledge. A half-crazed Karaite, Serach ben Nathan of Trok, who had an inclination to Rabbinical Judaism, in order to show his extensive knowledge, with mock humility laid before him a number of important questions, which Delmedigo was to answer offhand, and sent him a sable fur for the Polish winter.

Delmedigo found it to his advantage, in order to give himself the appearance of a distinguished character in Poland, to shroud himself in silence and seclusion. He at first answered Serach's questions not personally, but through one of his companions, an assistant and follower, Moses Metz. This man described his teacher as a choice intellect, a demi-god, who carried in his brain all human and divine knowledge. He sketched his appearance and character, his occupation and behavior, regulated, as he said, by higher wisdom, gave information about his descent from a learned and distinguished family on his father's and his mother's side, and, as his teacher's mouth-piece, imposed upon the credulous Karaite by saying that he had composed works on all branches of knowledge, at which the world would be astonished, if they came to light. Metz also communicated to Serach some of his teacher's theories in mathematics, religion, and philosophy, and thus still more confused Serach's mind. In his communications on Judaism, which Delmedigo either made himself or through Moses Metz, he was very cautious; here and there, it is true, he allowed a suggestion of unbelief to glimmer through, but quickly covered it over with a haze of orthodoxy. Only where he could do so without danger Delmedigo expressed his real opinion.

When he at last sent the Karaite an answer to a letter with his own hand (about 1621), he did not conceal his true views, but declared his preference for Karaism and its ancient teachers, loaded them undeservedly with praise, exalted science, and ridiculed the delusions of the Kabbala and its adherents. In the same letter to Serach, Delmedigo indulged in scoffs against the Talmud, and thought the Karaites fortunate that they were able to dispense with it. He had nothing to fear when he unburdened his heart before his Karaite admirer.

Delmedigo does not seem, on the whole, to have been at ease in Poland. He could not carouse with the nobles whom he attended professionally for fear of the Jews, and it was not possible to earn money in so poor a country. So he betook himself by way of Dantzic to Hamburg, where a Portuguese community had been lately permitted to settle. His knowledge of medicine seems to have met with little esteem in the city on the Elbe. What was his skill in comparison with that of the De Castros, father and son? He was compelled, in order to subsist, to undertake a certain amount of rabbinical duty, if only as preacher. For the sake of bread he had to play the hypocrite, and speak in favor of Rabbinical Judaism. Nay, in order to dissipate the rumor from Poland, which represented him as a heretic, he was not ashamed to praise the Kabbala, which he had shortly before condemned, as the highest wisdom, before which philosophy and all sciences must be dumb. For this purpose he prepared his defense of the secret doctrine, in refutation of the crushing arguments against it by one of his ancestors, Elias Del Medigo. His work was of the kind to throw dust in the eyes of the ignorant multitude; it displayed a smattering of learning on all sorts of subjects, but no trace of logic. He was too clever to maintain the sheepish style of dull, stupid credulity, and could not refrain from satire. He defended the genuineness of the Zohar as an ancient work by Simon bar Yochaï, or at least by his school. He argued that one must not be shocked by its many incongruities and absurdities; the Talmud also contains not a few, and is yet a sacred book. To save his reputation with the more intelligent, Delmedigo intimated that he had defended the Kabbala only from necessity. We must not, he says, superficially judge the character of an author by his words. He, for instance, was writing this defense of the Kabbala at the desire of a patron of high position, who was enamored of it. Should this friend come to be of another mind, and require an attack upon the Kabbala, he would not refuse him. In conclusion, he observes that philosophical students would no doubt ridicule him for having turned his back on wisdom, and betaken himself to folly; but he would rather be called a fool all his life than for a single hour transgress against piety.

This work, commenced in Hamburg, Delmedigo could not finish there. A pestilence broke out, and drove him, physician though he was, to Glückstadt. In this small community, where, as he said, there was neither town (Stadt) nor luck (Glück), he could find no means of subsistence, and he traveled on to Amsterdam about 1629. He could not attempt to practice medicine in a city where physicians lived of even higher eminence than at Hamburg, and so was obliged a second time to apply himself to the functions of rabbi. To show his importance, he printed his scientific replies to the questions of his Polish admirers, with the fulsome eulogies, clouds of incense, and foolish homage which the young Karaite Serach had offered him. It is a work of truly Polish disorder, in which mathematical theorems and scientific problems are discussed by the side of philosophical and theological questions, in a confused way. Delmedigo took care not to print his attacks upon the Kabbala and the Talmud, and his preference for the Karaites—in short, all that he had written to please the rich Serach. Instead of publishing an encyclopædic work which he boastfully said he had composed in his earliest youth, and which embraced all sciences and solved all questions, he produced a mere medley.

The Amsterdam community was then full of suspicion against philosophy and culture owing to the reckless behavior of Da Costa, and therefore Delmedigo thought it advisable to ward off every suspicion of unbelief, and get a reputation for strictest orthodoxy. This transparent hypocrisy did not answer well. He was, it is true, appointed preacher, and partially rabbi, in or near Amsterdam, but he could remain in Holland only a few years. Poor and unstable as he was, he went with his wife to Frankfort-on-the-Main about 1630 to seek means of subsistence. But here, in a German community, where Rabbinical learning was diffused, he could not obtain a rabbinical office; but he could turn his medical knowledge, scanty as it was, to account. As he felt no vocation for the office of rabbi, nor for medical practice, it was a matter of indifference if he changed the preacher's gown for the doctor's mantle. He was engaged, under irksome conditions, as communal doctor (February 14, 1631). How long he remained at Frankfort is not known; his position cannot have been favorable, for he removed to Prague (about 1648–1650), and in this most neglected community he settled. Later (1652) he was at Worms, probably only temporarily, and ended his life, which had promised so much, and realized so little, at Prague. Nor did he publish any part of his great work, which he had announced with so much pomposity.

In a measure Simone (Simcha) Luzzatto (born about 1590, died 1663) may be reckoned among the sceptics of this time. He was, at the same time as Leo Modena, rabbi in Venice. Luzzatto was not an eminent personage; but he had more solidity than his colleague Modena, or than Delmedigo. By the latter, who knew him personally, he was praised as a distinguished mathematician. He was also well read in ancient and modern literature. His uprightness and love of truth, which he never belied, distinguished him more than his knowledge and learning. A parable which Luzzatto wrote in Italian in his youth shows his views, as also his maturity of thought, and that he had reflected early on the relation of faith to science. He puts his thoughts into the mouth of Socrates, the father of Greek wisdom. At Delphi an academy had been formed to rectify the errors of human knowledge. Reason immediately presented a petition from the dungeon, where she had been so long kept by orthodox authority, to be set at liberty. Although the chief representatives of knowledge, Pythagoras and Aristotle, spoke against this request, and uttered a warning against her liberation, because, when free, she would produce and spread abroad most frightful errors, yet the academy set her at liberty; for by that means alone could knowledge be promoted. But the newly liberated minds caused great mischief; and the academicians were at a loss what to do. Then Socrates rose, and in a long speech explained that reason and authority, if allowed to reign alone, would produce only errors and mischief; but if mutually limited, reason by revelation, and revelation by reason, they mingle in the right proportion, and produce beautiful harmony, whereby man may attain his goal here below and hereafter. This thought, that reason and faith must regulate and keep watch over each other, which, in Maimuni's time had passed into a commonplace, was at this period, under the rule of Lurya's Kabbala, considered in Jewish circles a bold innovation.

Simone Luzzatto did not suffer himself to be ensnared by Kabbalistic delusions; he did not cast reason behind him; he was a believer, but withal sober-minded. He did not share the delusion of Manasseh ben Israel and others that the lost tribes of Israel were existing in some part of the world enjoying independence as a military power. With sober Jewish inquirers of former times, he assumed that Daniel's revelation does not point to a future Messiah, but only reflects historical events. He composed a work on the manners and beliefs of the Jews, which he proposed to exhibit "faithfully to truth, without zeal and passion." It was probably designed to form a counterpart to Leo Modena's representation, which cast a shadow on Judaism.