In Colonial Latin America the ‘República de Indios’ (Indians’ Commonwealth) had spaces of power recognized by the viceregal authorities. The ethnic lords or ‘caciques’ were mediators between their indigenous communities and different colonial actors and institutions requiring Indian labor and resources. In consequence, the ‘caciques’ enjoyed social prestige and colonial privileges in exchange for their brokerage and leadership. From this premise, the paper explores the attitudes and actions --and their relations with the spheres of power--, of the ‘caciques’ from the Indian communities of the 17th-century South Andean ‘Altiplano.’ What was the extent of their economic wealth? What were their interconnections with the regional elites? How their political position was eroded along the century? What was the impact on the ‘caciques’ of the biological process of ‘mestizaje’ (offspring of Spanish and Indian parents)? What about the impact of the concurrent process of ‘cultural mestizaje’? The main examples discussed are those of the ‘cacique’ families from the colonial province of Pacajes (South-East of Lake Titicaca): the Fernández Guarachi of Jesús de Machaca, and the Pacxipati of Tiahuanaco.