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Spanish colonization

New infectious diseases such as smallpox, endemic to the Europeans, caused high fatalities among the Amerindian population during the first decades of Spanish rule, as they had no immunity. At the same time, the natives were forced into the encomienda labor system for the Spanish. In 1563, Quito became the seat of a real audiencia (administrative district) of Spain and part of the Viceroyalty of Peru and later the Viceroyalty of New Granada.

The 1797 Riobamba earthquake, which caused up to 40,000 casualties, was studied by Alexander von Humboldt, when he visited the area in 1801–1802.

After nearly 300 years of Spanish rule, Quito still remained small with a population of 10,000 people. On 10 August 1809, the city's criollos called for independence from Spain (first among the peoples of Latin America). They were led by Juan Pío Montúfar, Quiroga, Salinas, and Bishop Cuero y Caicedo. Quito's nickname, " Luz de América " ("Light of America"), is based on its leading role in trying to secure an independent, local government. Although the new government lasted no more than two months, it had important repercussions and was an inspiration for the independence movement of the rest of Spanish America. Today, 10 August is celebrated as Independence Day, a national holiday.