Juan Ginés de Sepúlveda epitomizes in many ways, both personally and intellectually, the cosmopolitanism of Spanish political thought in the sixteenth century. Educated in Italy, disciple of Pomponazzi, translator of Aristotle, chronicler of the Emperor and mentor of his son Philip, Sepúlveda is best known—and often misunderstood as the defender of the more unsavory aspects of the Spanish conquest and colonization in America—for his bitter controversy with Bartolomé de las Casas. To that debate Sepúlveda brought a humanist's training and outlook anchored in his devotion to Aristotle, but strongly tempered by his attachment to Saint Augustine. It is the purpose of this paper to examine Sepúlveda's ideas on the nature of the American natives, particularly the question of whether the Indians are natural slaves. Considerations of space, of course, rule out the possibility of undertaking here a detailed scrutiny of the foundations upon which those ideas rest. It can be said, however, that they are typically Renaissance views, a blend of traditions characteristic of the composite nature of the age's intellectual milieu.