America as in what is now the United States? Disease was only a smaller part of their conquest of what is now the United States. Starting in 1540 to about 1500 the Spanish sent several ventures into New Mexico with soldiers and priests to 'settle' the new land. It got violent. In 1598 the Spanish sent an entrada, led by Juan Onate, in to what is now New Mexico, and settled Santa Fe. This was unlike the others as he brought with him not only soldiers and priests but civiliams that would be the first to settle in New Mexico. From that place they started the conquest of the region, using military and religion. The Spanish were able to subdue the Pueblos one at a time, the most dramatic battle taking place at Acoma. Acoma Pueblo is called sky city by some due to the Pueblo itself sitting on top of a mesa that has extremely sharp drops on almost all the sides. The Pueblo killed the nephew of the man leading the entrada, Juan De Zaldivar. As reprisal, the Spanish came back in larger forces led by De Zaldivar's brother Vincente (who really wanted revenge) and were able to breach the sharp rise to get to the city and defeat the Acoma. In the aftermath, - Per wiki ( I am cheating a bit I apologize - Some 500 prisoners were taken and later sentenced to a variety of punishments. Don Oñate ordered that every male above the age of twenty-five would have his right foot cut off and be enslaved for a period of twenty years. However, only twenty-four men actually received amputations. Males between the age of twelve and twenty-five were also enslaved for twenty years along with all of the females above the age of twelve. Many of these natives were dispersed among the residences of government officials or at Jesuit missions. Sixty of the youngest women were deemed not guilty and sent to Mexico City where they were "parceled out among Catholic convents". Two Hopi men were taken prisoner at the pueblo; after each had one of his hands cut off, they were released to spread the word of Spain's resolve.[3] This punishment really sent things home to the other Pueblos that resistance would be met with harsh punishment. With the Spanish came many priests, who came to spread Christianity to the Indians. With the military victory, now came the religion. The goal of the Priests was to truly stamp out Pueblo religion. The priests had the Pueblo religious houses torn down and had new Catholic churches built right on the top of the old religious houses. The work was done by the Pueblo Indians themselves, forced labor. after about 80 years of having their religion forced underground, an encomienda where the Pueblo had to pay taxes and other work for the Spanish, things were getting testy. The Pueblo Indians were not really digging life under Spanish rule. Then came the 1670s with a massive drought and attacks from Commanche warriors. Life went from miserable to intolerable for the Pueblo. Fed up, the Pueblo united and revolted against the Spanish, Killing most of the priest and forcing the Spanish to flee New Mexico for the safety of El Paso. It is probably the biggest victory for Indians in the history of the west. Sadly, it only lasted about 13 years and the Spanish came back. It was called a bloodless reconquest, but there was fights and battles. The Spanish were back and were not leaving. But they did learn from their lessons and the treatment of the native Indians was much different the second time around. Disease was part of it, but more military than anything in New Mexico.