Born at Motta, near [[Venice]. He studied at Venice, where he became acquainted with Erasmus and Aldus Manutius, and at an early age was reputed one of the most learned men of the time. In 1508 he went to Paris on the invitation of Louis XII as professor of belles lettres, and held for a time the position of rector in the university. Entering the service of Eberhard, prince-bishop of Liège, he was sent by that prelate on a mission to Rome, where Pope Leo X retained him, giving him (1519) the office of librarian of the Vatican. In the following year he went to Germany to be present as papal nuncio at the coronation of Charles V, and was also present at the diet of Worms, where he headed the opposition to Luther, advocating the most extreme measures to repress the doctrines of the reformer. His conduct evoked the fiercest denunciations of Luther, but it also displeased more moderate men and especially Erasmus. The edict against the reformer, which was finally adopted by the emperor and the diet, was drawn up and proposed by Aleandro. After the close of the diet the papal nuncio went to the Netherlands; where he kindled the flames of persecution, two monks of Antwerp, the first martyrs of the Reformation, being burnt in Brussels at his instigation. In 1523 Clement VII., having appointed him archbishop of Brindisi and Oria, sent him as nuncio to the court of Francis I. He was taken prisoner along with that monarch at the battle of Pavia (1525), and was released only on payment of a heavy ransom. He was subsequently employed on various papal missions, especially to Germany, but was unsuccessful in preventing the German princes from making a truce with the reformers, or in checking to any extent the progress of the new doctrines. He was created cardinal in 1536 by Paul III (at the same time as Reginald Pole) and died at Rome on the 1st of February 1542.
Aleandro compiled a Lexicon Graeco-Latinum (Paris, 1512), and wrote Latin verse of considerable merit inserted in M. Tuscanus's Carmina Illustrium Poetarum Italiorum. The Vatican library contains a volume of manuscript letters and other documents written by him in connexion with his various missions against Luther. They were utilized by Pallavicino in his Istoria del Concilio Tridentino (i. 23-28), who gives a very partial account of the Worms conference.
Aleandro, who is sometimes called "the elder," must be distinguished from his grand-nephew, also called Girolamo Aleandro (1574-1629). The younger Aleandro was a very distinguished scholar, and wrote Psalmi poenitentiales versibus elegiacis expressi (Treves, 1593), Gaii, veteris juris consulti Institutionum fragmenta, cum commentario (Venice, 1600), Explicatio veteris tabulae marmorcae solis effigie symbolisque exculptae (Rome, 1616).
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