In June and July 1975, Gastrointestinal illness occurred in more than 200 staff members and 2000 visitors to an American national park. In was characterized by prolonged diarrhea, cramps, nausea, and vomiting, lasted a median duration of 8 days, and was significantly associated with consumption of park water (P less than 0.001), which had been contaminated by raw sewage. Enterotoxigenic Escherichia coli serotype 06:K15:H16 was isolated from 20 of 49 ill park residents and from the park's water supply, but not from 71 residents who had never been ill or had been well for at least 4 days. No other bacterial, viral, or parasitic pathogens were isolated from ill or well persons. This outbreak is the first waterborne epidemic of diarrheal illness shown to be due to enterotoxigenic. E. coli, and this study documents one mode of transmission of this pathogen. This investigation also suggests the relative insensitivity of current methods for identifying persons infected with this organism, either by the culturing of randomly selected isolates or by measuring serologic responses.