Francesco I (25 March 1541 – 19 October 1587) was the second Grand Duke of Tuscany, ruling from 1574 until his death in 1587, a member of the House of Medici. Born in Florence, he was the son of Cosimo I de' Medici, Grand Duke of Tuscany, and Eleanor of Toledo. He served as regent for his father Cosimo after he retired from his governing duties in 1564. On 18 December 1565, he married Joanna of Austria, youngest daughter of Holy Roman Emperor Ferdinand I and his wife Anne of Bohemia and Hungary, after Princess Elizabeth of Sweden, among others, had been considered. By all reports, it was not a happy marriage. Joanna was homesick for her native Austria, and Francesco was neither charming nor faithful. Joanna died at the age of thirty-one in 1578. Soon after Grand Duchess Joanna had died, Francesco went on to marry his Venetian mistress, Bianca Cappello, after aptly disposing of her husband, a Florentine bureaucrat. Because of the quick remarriage and similar occurrences among the Medici (Francesco's younger brother Pietro had reportedly killed his wife), rumours spread that Francesco and Bianca had conspired to poison Joanna. Francesco reportedly built and decorated the Villa di Pratolino for Bianca. She was, however, not always popular among Florentines. They had no legitimate children, but Bianca had borne him a son, Antonio (29 August 1576 – 2 May 1621), in his first wife's lifetime. Following the death of Francesco's legitimate son Filippo in 1582, Antonio was proclaimed heir. Like his father, Francesco was often despotic, but while Cosimo had known how to maintain Florentine independence, Francesco acted more like a vassal of the Habsburgs of Austria and Spain. He continued the heavy taxation of his subjects to pay large sums to the empire. He had an avid interest in manufacturing and sciences. He founded porcelain and stoneware manufacture, but these did not thrive until after his death. He continued his father's patronage of the arts, supporting artists and building the Medici Theater as well as founding the Accademia della Crusca. He was also passionately interested in chemistry and alchemy and spent many hours in his private laboratory. Francesco and Bianca died on 19 and 20 October, both at the Medici Villa in Poggio a Caiano. Although the original death certificates mention malaria, it has been widely speculated that the couple was poisoned. Francesco was succeeded by his younger brother Ferdinando.

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