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In the Iberian Peninsula the impetus of the counteroffensive against the Moors carried the Portuguese to probe the West African coastline and the Spanish to attempt the expulsion of Islam from the western Mediterranean. In the last years of the 15th century, Portuguese navigators established the sea route to India and within a decade had secured control of the trade routes in the Indian Ocean and its approaches. Mercantile interests, crusading and missionary zeal, and scientific curiosity were intermingled as the motives for this epic achievement. Similar hopes inspired Spanish exploitation of the discovery by Christopher Columbus of the Caribbean outposts of the American continent in 1492. The Treaties of Tordesillas and Saragossa in 1494 and 1529 defined the limits of westward Spanish exploration and the eastern ventures of Portugal. The two states acting as the vanguard of the expansion of Europe had thus divided the newly discovered sea lanes of the world between them.

By the time of the Treaty of Saragossa, when Portugal secured the exclusion of Spain from the East Indies, Spain had begun the conquest of Central and South America. In 1519, the year in which Ferdinand Magellan embarked on the westward circumnavigation of the globe, Hernán Cortés launched his expedition against Mexico. The seizure of Peru by Francisco Pizarro and the enforcement of Portuguese claims to Brazil completed the major steps in the Iberian occupation of the continent. By the middle of the century, the age of the conquistadores was replaced by an era of colonization, based both on the procurement of precious metal by Indian labour and on pastoral and plantation economies using imported African slaves. The influx of bullion into Europe became significant in the late 1520s, and from about 1550 it began to produce a profound effect upon the economy of the Old World.