NARRATOR: Since the Americas had existed in isolation since the Ice Age, those first European explorers who began coming in 1992 initiated a cultural exchange that would have profound repercussions for both sides. The Indians would be brought to the brink of extinction. The Europeans would benefit enormously from an introduction to Indian crops and animals.

- The American plants have a tremendous impact on the old world because they're so much more productive than the plants on which the old world relied. So what they called maize, what we call corn really transformed cuisines all over Europe and Africa and even into China. And sweet potatoes spread into Asia almost immediately. Other kinds of foods like tomatoes, peppers, it transformed food ways and populations because it made it possible to sustain much larger populations.

NARRATOR: In return, the Europeans unintentionally carried over smallpox, yellow fever, malaria, and influenza, diseases that would nearly wipe out Indian populations throughout the Americas.

- Diseases that were endemic in the entire rest of the world were unknown here, and that's why the epidemics of diseases brought by Europeans were so devastating to the Indians. And even the common cold or flu could destroy whole villages.

NARRATOR: The result was a massive reduction in the Indian population over a relatively short period of time.

- We actually don't know the size of the population here before the Europeans came because so much of this happened before settlement. It happened from the earliest contacts. But many demographers have estimated populations were 90% smaller at the end of the first century of contact than they were at the beginning. So the impact was tremendous.

NARRATOR: Those left behind were vulnerable. Their communities were devastated. Their beliefs were shattered.

KAREN ORDAHL KUPPERMAN: The fact that their traditional healing techniques were not working, the fact that the Europeans did not get sick or certainly not in the same numbers in the same way created this kind of psychological crisis, I think, as well as a physical one. The question of why have the gods deserted us. That's a sort of extreme way of putting it. But I think that must have been the way they saw it.