Lorenzo's hopes of a strong coalition against his foe were destroyed by the assassination of Sforza of Milan in 1474. The Duke was murdered in the church of St Stephen by three young nobles who had personal injuries to avenge and were also inspired by an ardent desire for republican liberty. The Pope exclaimed, when he heard the news, that the peace of Italy was banished by this act of lawlessness. Lorenzo, disapproving of all outbreaks against tyranny, promised to support the widowed Duchess of Milan. The control he exercised during her brief régime came to an end in 1479 with the usurpation of Ludovico, her Moorish brother-in-law.

Then Riario, the Pope's nephew, saw that the time was ripe for a conspiracy against the Medici which might deprive them of their power in Italy. He allied himself closely with Francesco dei Pazzi, who was anxious for the aggrandisement of his own family. His name had long been famous in Florence, every good citizen watching the ancient Carro dei Pazzi which was borne in procession at Easter-tide. The car was stored with fireworks set alight by means of the Colombina (Dove) bringing a spark struck from a stone fragment of Christ's tomb. The citizens could not forget the origin of the sacred flame, for they had all heard in youth the story of the return of a crusading member of the Pazzi house with that precious relic.

The two conspirators hoped to bring a foreign army against Florence and, therefore, gained the aid of Salviati, Archbishop of Pisa. The Pope bade them do as they wished, "provided that there be no killing." In reality, he was aware that a plot to assassinate both Lorenzo dei Medici and his brother, Giuliano, was on foot, but considered that it would degrade his holy office if he spoke of it.

It was necessary for their first plan that Lorenzo should be lured to Rome where the conspirators had assembled, but he refused an invitation to confer with the Pope about their differences and a new plan had to be substituted. Accordingly the nephew of Riario, Cardinal Raffaelle Sansoni, expressed a keen desire to view the treasures of the Medici household, and was welcomed as a guest by Florence. He attended mass in the Cathedral which was to be the scene of the assassination, since Lorenzo and his brother were certain to attend it. Two priests offered to perform the deed of sacrilege from which the original assassin recoiled. They hated Lorenzo for his treatment of Volterra, and drove him behind the gates of the new sacristy. Giuliano was slain at the very altar, his body being pierced with no less than nineteen wounds, but Lorenzo escaped to mourn the fate of the handsome noble brother who had been a model for Botticelli's famous "Primavera."

He heard the citizens cry, "Down with traitors! The Medici! The Medici!" and resolved to move them to a desperate vengeance on the Pazzi. The Archbishop of Pisa was hanged from the window of a palace, while a fellow-conspirator was hurled to the ground from the same building. This gruesome scene was painted to gratify the avengers of Giuliano.

Florence was enthusiastic in defence of her remaining tyrant. He was depicted by Botticelli in an attitude of triumph over the triple forces of anarchy, warfare and sedition. All the family of Pazzi were condemned as traitors. Their coat of arms was erased by Lorenzo's adherents wherever it was discovered.

Henceforth, Lorenzo exercised supreme control over his native city. He won Naples to a new alliance by a diplomatic visit that proved his skill in foreign negotiations. The gifts that came to him from strange lands were presented, in reality, to the master of the Florentine "republic." Egypt sent a lion and a giraffe, which were welcomed as wonders of the East even by those who did not appreciate the fact that they showed a desire to trade. It was easy soon to find new markets for the rich burghers whose class was in complete ascendancy over the ancient nobles.

Lorenzo was seized with mortal sickness in the early spring of 1492, and found no comfort in philosophy. He drank from a golden cup which was supposed to revive the dying when it held a draught, strangely concocted from precious pearls according to some Eastern fancy. But the sick man found nothing of avail in his hour of death except a visit from an honest monk he had seen many times in the cloisters of San Marco.

Savonarola came to the bedside of the magnificent pagan and demanded three things as the price of absolution. Lorenzo was to believe in the mercy of God, to restore all that he had wrongfully acquired, and to agree to popular government being restored to Florence. The third condition was too hard, for Lorenzo would not own himself a tyrant. He turned his face to the wall in bitterness of spirit, and the monk withdrew leaving him unshriven.

The sack of Volterra, and the murder of innocent kinsfolk of the Pazzi who had been involved in the great conspiracy haunted Lorenzo as he passed from life in the prime of manhood and glorious achievements. He would have mourned for the commerce of his city if he had known that in the same year of 1492 the discovery of America would be made, through which the Atlantic Ocean was to become the highway of commerce, reducing to sad inferiority the ports of the Mediterranean.