Two regions in the Americas were home to advanced civilizations prior to the European conquest: Mesoamerica and the Andean region. Mesoamerica, which is the focus of this exhibit, ranged from central Mexico to northern Central America, including Guatemala, Belize, and part of Honduras. Further to the south, the Andean Region, home to the great Inca Empire, extended (along the lines of the Andean Mountains) from Quito, Ecuador, to the northern part of Chile.

Mesoamerica was populated by 25 million people at the time of the arrival of the Spaniards in 1519. Scholars studying the region classify its history into three periods: the Formative or Pre-classical (1500 B.C.-300 A.D.), Classical (300-900 A.D.), and Post-Classical (900-1519 A.D.). "Classical" refers to the pinnacle of Mesoamerican culture. During that period, extraordinary cities such as Teotihuacán, Tula, Monte Albán, Palenque, Tikal, and others flourished. Scholars still debate why such cities were abandoned; perhaps it was due to wars or agriculture failures. Later, other cities emerged. The Aztecs founded the great city of Tenochtitlán in 1325 on the site of what is now downtown Mexico City; they established an extensive empire over the span of two centuries. Important city-states during the Post-Classical period were Chichén-Itzá and Mitla.

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