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The implementation of treated municipal water systems in the 20th century led to a dramatic decrease in waterborne disease in the United States. However, communities with deficient water systems still experience waterborne outbreaks. In August 2004, we investigated an outbreak of gastroenteritis on South Bass Island, Ohio, an island of 900 residents that is visited by>500,000 persons each year.To identify the source of illness, we conducted a case-control study and an environmental investigation. A case was defined as diarrhea in a person who traveled to the island during the period from May 1 through 30 September 2004 and became ill within 2 weeks after the visit. Healthy travel companions served as matched control subjects. We also performed an environmental assessment and extensive testing of island water sources.Among the 1450 persons reporting illness, Campylobacter jejuni, norovirus, Giardia intestinalis, and Salmonella enterica serotype Typhimurium were identified in 16, 9, 3, and 1 persons, respectively. We interviewed 100 case patients and 117 matched control subjects. Case patients were more likely to drink water on the island than control subjects (68% vs. 35%; matched odds ratio, 4.3; 95% confidence interval, 2.2–9.3). Sampling of ground water wells indicated contamination with multiple fecal microbes, including Escherichia coli, C. jejuni, Salmonella species, and Giardia species. Irregularities in sewage disposal practices that could have contaminated the underground aquifer were noted.The combined epidemiological and environmental investigation indicated that sewage-contaminated ground water was the likely source of this large outbreak. Long-term changes to the island's water supply and sewage management infrastructure are needed.