Campylobacter species infections are a common cause of acute gastroenteritis, and may uncommonly be complicated by renal, neurological, and rheumatologic sequelae. Although excess summertime campylobacteriosis has been observed, environmental mechanisms driving disease seasonality are poorly understood. We sought to evaluate the relationship between environmental factors and campylobacteriosis risk in a major North American metropolitan area. We evaluated 1532 cases of campylobacteriosis reported in Philadelphia between 1994 and 2007. We constructed Poisson regression models with oscillatory smoothers, and also used case-crossover design, to evaluate the associations between environmental exposures and disease risk on weekly and daily time scales. Both methods control for confounding by seasonally oscillating environmental factors. Incidence was greatest in June and July, with annual periodicity. Weekly incidence was associated with increasing relative humidity, (incidence rate ratio (IRR) per % 1.017, 95% CI 1.008-1.025), temperature (IRR per degrees C 1.041, 95% CI 1.011-1.072), and decreasing Delaware River temperature during the same week (IRR per degrees C 0.922, 95% CI 0.883-0.962), and at 4-week lags (IRR per degrees C 0.953, 95% CI 0.919-0.990). No acute associations were identified in case-crossover analyses. Our findings affirm the summertime seasonality of campylobacteriosis in Philadelphia, and the link between warm, humid weather and disease risk. However, the link between low river temperatures and enhanced campylobacteriosis risk in humans described here is novel, consistent with known links between watershed temperature and Campylobacter survival, and implicates local watersheds as epidemiologically important reservoirs for foodborne pathogens.