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Diarrhea remains a common complaint among US patients who seek medical attention.We performed a prospective study to determine the etiology of diarrheal illness among patients and control subjects of all ages presenting to the emergency departments and outpatient clinics of 2 large academic hospitals in Baltimore, Maryland, and New Haven, Connecticut. We used molecular methods to detect the presence of diarrheagenic Escherichia coli pathotypes, including enteroaggregative E. coli (EAEC), as well as Shiga toxin-producing, cytodetaching, enterotoxigenic and enteropathogenic E. coli.Of the pathotypes sought, only EAEC was found in an appreciable proportion (4.5%) of case patients, and it was found more frequently among case patients than control subjects (P < .02). Surprisingly, EAEC was the most common bacterial cause of diarrhea in our population. EAEC was common in all age strata and was not associated with foreign travel or immunodeficiency. EAEC infection is frequently accompanied by fever and abdominal pain, though this did not happen more frequently in patients with EAEC infection than in patients with diarrhea due to other causes.Our data suggest that EAEC infection should be considered among persons with diarrhea that does not yield another known etiologic agent.