The Spanish had established the town of Santa Cruz de la Sierra in the north of the territory claimed by Portugal in 1561, and from here plant missions in the Mamore-Guapore Basin in about 1682.

Called the Mojos and Chiquitos, these mission provinces are in what is now low-land Bolivia fronting on the states of Mato Grosso and Rondonia.

By 1746 there are twenty-four mission towns in the Mojos and ten in Chiquitos.

The bandeirantes again carry the flag of Portugal into the region, first attacking the Chiquitos missions for slaves and then discovering gold in Mato Grosso (1718-36).

Unsure where these gold discoveries are in relation to the Spanish territories, the members of the Lisbon-based Overseas Council, which administers the colonies, order a comprehensive reconnaissance and the drawing of accurate maps.

Francisco de Melo Palheta leads an expedition from Belem to the Guapore in 1723, reporting to Lisbon the startling news about the numerous prosperous Jesuit missions.

Native resistance delays the conquest and settlement of the Bolivian lowlands.

The Spanish establish Santa Cruz de la Sierra (hereafter, Santa Cruz) in 1561, but the Gran Chaco, the colonial name for the arid Chaco region, remains a violent frontier throughout colonial rule.

In the Chaco, the natives, mostly Chiriguano, carry out unrelenting attacks against colonial settlements and remain independent of direct Spanish control.

Nuflo de Chávez, a Spanish captain whose legacy is the expansion of colonization through virgin rainforest and savanna areas in southeastern South America, had begun his campaign in Buenos Aires,Argentina's capital city, to the second biggest settlement, Asunción, Paraguay's capital city, and finishing with the last of the larger settlements, Santa Cruz de la Sierra, located about three hundred and forty miles (fibe hundred and fifty kilometers) east of La Paz, in 1561.

Named by Chávez in honor of his beloved native city in Extremadura, Spain, the "Holy Cross of the Hills" is today the capital city of the Santa Cruz department in eastern Bolivia.

The municipality's population was 1,528,683 inhabitants in 2006 (official estimate) and the urban population is 1,545,161 in 2008 (official estimate), making Santa Cruz, as it is commonly known, the largest city in Bolivia.