In the summer of 1991 a large outbreak of Escherichia coli O157:H7 associated diarrhea occurred in 6 Inuit communities in the Canadian Northwest Territories. The total population of these communities is 5,292. Of the 521 individuals who developed diarrhea, 152 (29%) were positive for E. coli O157:H7 on stool culture or positive by verotoxin analysis. Median age was 6 years. The attack rate for children < 1 year was 43% in the major affected community of Arviat. Hemolytic-uremic syndrome (HUS) developed in 22 cases, and 2 patients died. Asymptomatic stool carriage of verotoxin-producing E. coli (VTEC) 2-5 weeks after diarrheal illness was noted in 4/28 persons followed prospectively. Epidemic curves, case-control studies and phage type testing suggested person-to-person transmission. The original source of infection was not identified, though a food source was suspected. VTEC were detected in 6 food samples (minced beef and caribou) taken from retail outlets and homes. Primary prevention of infection through health education and promotion activities, as well as long-term follow-up of HUS survivors, are indicated in this population.