The presence of Yaws and the time-course for its replacement by syphilis were investigated in upper New York State to assess Yaws as the original North American treponemal disease and to document the timing of the first origins of syphilis in this region. Skeletal remains from Frontenac Island [2000 years before present (ybp)], Sackett (700-1000 ybp), Tram (1570-1590), and Powerhouse (1635-1655) sites were evaluated. Periosteal reaction was found in Frontenac Island, Sackett and Tram site skeletons, in contrast to the characteristic changes of syphilis in 12% from the Powerhouse site. Treponemal disease has clearly existed for at least 2000 years in what became upstate New York. The characteristics of the initial treponemal disease (Yaws) remained essentially unchanged for most of that time, at least through 1590. Subsequent to European contact, the character of the treponemal disease changed drastically, and syphilis was identified. The implication is that European contact resulted in significant change in disease expression