One important cause of Native American depopulation during European contact was epidemic disease. The sixteenth through nineteenth centuries saw many different diseases strike Native American populations with considerable frequency.






Many of the diseases, such as syphilis, smallpox, measles, mumps, and bubonic plague, were of European origin, and Native Americans exhibited little immunity because they had no previous exposure to those diseases. This caused greater mortality than would have occurred if these diseases been endemic to the Americas.