The first in depth study of the demographic effects of the Spanish conquest. Cook estimated population size on the basis of archaeology, carrying capacity of the agricultural systems, disease mortality, depopulation ratios, and census projection. He also analyzed the catastrophic population decline that resulted from contact with Europeans, and compared this experience with that of the coastal region and the Andean highlands.

"The biological mingling of the previously separated Old and New Worlds began with the first voyage of Columbus. The exchange was a mixed blessing: It led to the disappearance of entire peoples in the Americas, but it also resulted in the rapid expansion and consequent economic and military hegemony of Europeans. Amerindians had never before experienced the deadly Eurasian sicknesses brought by the foreigners in wave after wave; smallpox, measles, typhus, plague, influenza, malaria, yellow fever. These diseases conquered the Americas before the sword could be unsheathed. From 1492 to 1650, from Hudson's Bay in the north to southernmost Tierra del Fuego, disease weakened Amerindian resistance to outside domination. The Black Legend, which attempts to place all of the blame for the injustices of conquest on the Spanish, must be revised in light of the evidence that all Old World peoples carried, literally though largely unwittingly, the germs of the destruction of American civilization" (publisher).