The high frequency of late prehistoric New World treponemal disease is attributable to the demographic changes concomitant with the adoption of agriculture. However, these demographic changes in group mobility and site density episodically preceded intensive plant domestication, suggesting possible staggered temporal change in observed treponemal disease case frequency. Thirteen convincing and an additional two probable (N = 581) cases of treponemal disease were identified in an eight-site skeletal sample spanning the Middle (6000–3000 BCE) to Late (2500–ca. 1000 to 500 BCE) Archaic and Early Woodland (500 BCE–0 CE) periods from the western Tennessee River Valley. Treponemal disease cases are infrequent in both the Middle (3/115, 2.6%) and Late (2 to 4 cases, ≤1%, N = 378) Archaic horizons, and more frequent (8/88, 9.1%) in the Early Woodland horizon. As the subsistence economy across the Archaic-Woodland temporal boundary in the western Tennessee River Valley remained, as elsewhere, based on intensive hunting and collecting, the demographic corollaries of treponemal disease would apparently not be met. However, the traditional horizon marker of the Woodland period is the adoption of pottery, an activity associated with sedentism. Am J Phys Anthropol 131:205–217, 2006. © 2006 Wiley-Liss, Inc.