AbstractMany of the lesions found in American Indian bones do not resemble those found in human bones from the Old World, suggesting that the American Indians suffered from a distinct group of illnesses. If Old World pathogens did not follow man to the New World, what were the sources of pre‐Columbian Indian diseases? As in the Old World, humans were susceptible to diseases endemic in the local animal populations. Exposure to these diseases varied with culturally conditioned animal contacts. As the New World population increased, the probability for disease increased, to the point where it is likely that even in pre‐Columbian times, disease rather than war or climatic changes may have been a major influence in changing settlement patterns. The generalization that the only Old World plants and animals found in the New were those brought by man seems to hold as true for the pre‐Columbian disease organisms as it is for larger forms of life.