OBJECTIVE: To evaluate risk factors for childhood hemolytic-uremic syndrome (HUS) and gastroenteritis during an epidemic of Escherichia coli O157:H7 infection. DESIGN: Case-control study. SETTING: Remote Inuit community of Arviat in northern Canada. PARTICIPANTS: Of the 565 Arviat residents less than 15 years of age, 19 had HUS and 65 more had E. coli O157:H7 gastroenteritis. The 19 children with HUS were compared with 19 age- and gender-matched children with uncomplicated E. coli O157:H7 gastroenteritis, and both HUS and gastroenteritis patients were compared with 19 healthy control subjects. INTERVENTIONS: Questionnaire administered face-to-face to parents of participants in the home. MAIN OUTCOME MEASURES: Rates of exposure to foods, travel, sources of water, and gastrointestinal illness in family members. RESULTS: Patients with HUS and those with uncomplicated E. coli O157:H7 gastroenteritis differed only on measures of clinical severity. In the 7 days before the onset of gastrointestinal symptoms, children with HUS and those with uncomplicated gastroenteritis were more likely to have been exposed to a family member with diarrhea than were the healthy control subjects (odds ratio = 9 for HUS vs healthy control subjects; 95% confidence interval 2 to 43; p < 0.01). Undercooked ground meat and foods traditionally consumed by the Inuit were not implicated as risk factors in E. coli O157:H7 infection. CONCLUSIONS: These findings emphasize the potential for extensive intrafamilial transmission of verotoxin-producing E. coli once infection is introduced into certain communities.