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The Mendozas in the 16th Century
The family loyalty demonstrated by Santillana's children did not persist through the next generation. With the cardinal dead, the family's leadership fell back in power under the constable of Castilla living in Burgos, Bernardino Fernández de Velasco, Santillana's son, an anomaly according to historian, to the detriment of Íñigo López de Mendoza y Luna, Duke of the Infantado, whose house was in Guadalajara. Bernardino would be the one to guide Mendoza throughout the critical years, in which the crown went from the Trastámara to the Habsburgo. But the constable found himself at the front of Mendozas who were less willing to follow orders from a sole leader. The same dimensions of power that the cardinal had assured the young generation of the family allowed its members to undertake more independent political careers.

Decline and fall
The Palace of Infantado in Guadalajara did not cease to make up the family's material centre. The Mendozas that stayed in Castilla accepted the constable's leadership, but even in this group disputes surfaced, especially between the Infantado and the Count of Coruña, who weakened the family's cohesion as a political and military unit. The family unit was even more threatened by the acts of two of Santillana's grandson: the cardinal's eldest son Rodrigo, marquis of the Cenete, and the second Count of Tendilla.

Rodrigo Díaz de Vivar y Mendoza
The marquis of Cenete and the Count of Cid acted, in all aspects, totally independent from the Mendoza group, stimulated by their haughty and arrogant character. From his bases in granada where, thanks to his father—the cardinal—he possessed vast domains, he occupied the post of prison governor of Guadix and came to form part of the Council of Granada. Cenete developed a career marked by audacity, opportunism, and scandal. In 1502 he secretly married and in 1506 he kidnaped the woman with home Isable the Catholic had forbidden him from marrying. In 1514 he was accused by the Crown of entering the city of Valencia completely armed, without royal sanction, and in 1523 he joined forces with his younger brother, the Count of Mélito, once again without permission, to quell the revolt of the thieves' slang. In 1535, his second daughter, heiress to the title and fortune, married the heir of the Count of Infantado, returning the titles to the central house of the Mendozas.

Diego Hurtado de Mendoza
The career of Diego Hurtado de Mendoza, count of Mélito and older brother to the Marquis of Cenete, presents totally different features. Mélito carried out a moderately important role as viceroy of Valencia during the first years of Charles V's reign, in the uprisings and control of the thieves' slang.

Ana de Mendoza y de la Cerda
Granddaughter of the Count of Mélito, she married Ruy Gómez de Silva, the favourite of Felipe II, in 1553. The couple, who in 1559 received the title of Princes of Éboli, became the centre of a political party in the Court. Before the politics of the Duke of Alba of a "closed Spain", the Mendozas were promoters of a Spain "open" to new ideas.

The period, marked by the ascending politics of the Éboli in Castilla, that goes from 1555 until the death of Ruy Gómez in 1573. This politics of an "open Spain" was not typical of the House of Mendoza as a whole, but rather of the branches of the family that came from the cardinal Mendoza, for which he had created proper bases of power in the kingdoms of Granada and Valencia.

Íñigo López de Mendoza y Quiñones
The most famous and capable of Santillana's grandsons was the second Count of Tendilla. Thanks to his uncle's influence, the cardinal of Mendoza, Tendilla was named captain general of the kingdom of Granada and prison governor of Alhambra. He was capable of dazzling gestures like his cousin the marquis of cenete, but was intensely loyal to Fernando the Catholic: during the disputes about the succession that arose after 1504, he was one of the only noble Castillians that remained loyal to Fernando and was opposed to the efforts of Felipe I of Castilla to be done with the kingdom.

Each time more absorbed in the problems of the kingdom of Granada, Tendilla isolated himself from the rest of his family. The results were an intensification of his conservative standings and his conviction that his house was the only one that remained loyal to the family traditions of the Mendozas.

Lope Hurtado de Mendoza
Born in 1499, he was the youngest son of Juan Hurtado Díaz de Mendoza y Salcedo, Lord of Legarda, Salcedo, and the Bujada, major of Vizcaya. Since he was not the heir to the title of major he was sent to Court, were he prospered and came to occupy important positions, being named as member of the Council of the Kingdom and Main Butler of Margarita de Austria. He served also as governor of Orán and ambassador before the courts of Portugal, Germany, and Rome. He inherited from his father the Lordship of the Bujada and in 1539 he was named commander of the charge of Villarubia de Ocaña by the emperor Carlos V. He was first married to Teresa Ugarte, heiress to the Lordship of Astobiza. His second wife was margarita de Rojas, with whom he had Fernando de Mendoza, who was distinguished for his career and the military and came to be General of the coast of Granada and Knight Commander of Sancti Spiritus in Alcántara. He died in October of 1558.