BACKGROUND: Perfluorooctanoic acid (PFOA) is considered a probable human carcinogen by the U.S. Environmental Protection Agency. It does not exist in nature but has been used widely since World War II. It is present in the serum of most Americans at about 4-5 ng/mL, although the routes of exposure remain unknown. OBJECTIVES: We examined predictors of PFOA in mid-Ohio Valley residents living near a chemical plant that until recently released large quantities of PFOA into the environment, contaminating drinking water. METHODS: We studied 69,030 residents in six contaminated water districts who participated in a 2005-2006 survey involving a questionnaire and blood tests. Of these, 64,251 had complete data on PFOA and covariates. We also analyzed a subset (71%) for whom we had occupational history. We ran linear regression models to determine serum PFOA predictors. RESULTS: Mean PFOA serum level was 83.0 ng/mL (median, 28.2). The most important predictors were current (median for all districts, 38.4; highest district, 224.1) and past (median, 18.6) residence in contaminated water districts, and current (median, 147.8) and past (median, 74.9) employment at the chemical plant (R(2) model = 0.55). PFOA was higher for males, those consuming local vegetables, and those using well water rather than public water, and lower for those using bottled water. PFOA was higher at younger and older ages. CONCLUSIONS: PFOA levels in this population varied with distance of residence from the plant and employment at the plant. Effects of age and sex reflected prior findings. Effects of other demographic and lifestyle covariates were relatively weak.