In June 1998, we investigated one of the largest foodborne outbreaks of enterotoxigenic Escherichia coli gastroenteritis reported in the United States.We conducted cohort studies of 11 catered events to determine risk factors for illness. We used stool cultures, polymerase chain reaction, and serologic tests to determine the etiologic agent, and we conducted an environmental inspection to identify predisposing conditions and practices at the implicated establishment.During 5-7 June, the implicated delicatessen catered 539 events attended by >16,000 people. Our epidemiological study of 11 events included a total of 612 attendees. By applying the median prevalence of illness (20%) among events with ill attendees to the total number of events with any ill attendees, we estimate that at least 3300 persons may have developed gastroenteritis during this outbreak. Multiple food items (potato salad, macaroni salad, egg salad, and watermelon) were associated with illness, all of which required extensive handling during preparation. Enterotoxigenic Escherichia coli serotype O6:H16 producing heat-labile and heat-stable toxins was isolated from the stool specimens from 11 patients. Eight patients with positive stool culture results, 11 (58%) of 19 other symptomatic attendees, and 0 (0%) of 17 control subjects had elevated serum antibody titers to E. coli O6 lipopolysaccharide. The delicatessen had inadequate hand-washing supplies, inadequate protection against back siphonage of wastewater in the potable water system, a poorly draining kitchen sink, and improper food storage and transportation practices.In the United States, where enterotoxigenic Escherichia coli is an emerging cause of foodborne disease, enterotoxigenic Escherichia coli should be suspected in outbreaks of gastroenteritis when common bacterial or viral enteric pathogens are not identified.