OBJECTIVE: To define the epidemiologic features of childhood hemolytic-uremic syndrome (HUS) on a national level in Canada, to determine the proportion of patients in whom Escherichia coli O157:H7 was isolated from stools, and to examine risk factors for more severe HUS. DESIGN: From January 1986 to December 1988, patients with HUS were reported prospectively to the Canadian Pediatric Kidney Disease Reference Centre, a national registry for pediatric renal disorders, or were identified retrospectively through a medical records search at participating institutions. SETTING: All children's hospitals in Canada and the children's wards of general hospitals in Canadian cities with populations greater than 350,000. PATIENTS: Two hundred twenty-six children, including 126 girls. MEASUREMENTS AND MAIN RESULTS: The average annual incidence of HUS in children younger than 15 years was 1.44 per 100,000; the peak age-specific incidence was 3.11 per 100,000 younger than 5 years. The incidence of HUS varied by region; the risk of HUS in Alberta was 2.9 times that in Ontario (p less than 0.0001). Of the 169 patients whose stools were screened, E. coli O157:H7 was isolated in 87 (51%). Risk factors for prolonged dialysis or death included young age, seizures, elevated white blood cell count at admission to hospital, and shorter, more severe prodromal illness. The rate of dialysis was higher in female patients (55% vs 39%; p = 0.02). CONCLUSIONS: HUS is relatively common in Canadian children younger than 5 years, and is strongly associated with E. coli O157:H7 infection. Reasons for the striking regional variation in the incidence of HUS and for the increased rate of dialysis in female patients are unexplained and deserve further investigation.