In these circumstances Ippolito had not strength of character to sacrifice himself for the consolidation of the Medicean power, which could only have been effected by maintaining a close bond of union between its members. The death of Clement in 1534 obscured his prospects in the Church. He was still too young to intrigue for the tiara. The new Pope, Alessandro Farnese, soon after his election, displayed a vigour which was unexpected from his age, together with a nepotism which his previous character had scarcely warranted. The Cardinal de’ Medici felt himself excluded and oppressed. He joined the party of those numerous Florentine exiles, headed by Filippo Strozzi, and the Cardinals Salviati and Ridolfi, all of whom were connected by marriage with the legitimate Medici, and who unanimously hated and were jealous of the Duke of Civita di Penna. On the score of policy it is difficult to condemn this step. Alessandro’s hold upon Florence was still precarious, nor had he yet married Margaret of Austria. Perhaps Ippolito was right in thinking he had less to gain from his cousin than from the anti-Medicean faction and the princes of the Church who favoured it. But he did not play his cards well. He quarrelled with the new Pope, Paul III., and by his vacillations led the Florentine exiles to suspect he might betray them.
In the summer of 1535 Ippolito was at Itri, a little town not far from Gaeta and Terracina, within easy reach of Fondi, where dwelt the beautiful Giulia Gonzaga. To this lady the Cardinal paid assiduous court, passing his time with her in the romantic scenery of that world-famous Capuan coast. On the 5th of August his seneschal, Giovann’ Andrea, of Borgo San Sepolcro, brought him a bowl of chicken-broth, after drinking which he exclaimed to one of his attendants, ‘I have been poisoned, and the man who did it is Giovann’ Andrea.’ The seneschal was taken and tortured, and confessed that he had mixed a poison with the broth. Four days afterwards the Cardinal died, and a post-mortem examination showed that the omentum had been eaten by some corrosive substance. Giovann’ Andrea was sent in chains to Rome; but in spite of his confession, more than once repeated, the court released him. He immediately took refuge with Alessandro de’ Medici in Florence, whence he repaired to Borgo San Sepolcro, and was, at the close of a few months, there murdered by the people of the place. From these circumstances it was conjectured, not without good reason, that Alessandro had procured his cousin’s death; and a certain Captain Pignatta, of low birth in Florence, a bravo and a coward, was believed to have brought the poison to Itri from the Duke. The Medicean courtiers at Florence did not disguise their satisfaction; and one of them exclaimed, with reference to the event, ’We know how to brush flies from our noses!’