Objective: To determine whether circumcision decreases the risk of symptomatic urinary tract infection (UTI) in boys less than 5 years of age. Study design: A case-control study (1993 to 1995) in the setting of a large ambulatory pediatric service. Case subjects and control subjects were drawn from the same population. One hundred forty-four boys less than 5 years of age (median age, 5.8 months) who had a microbiologically proven symptomatic UTI (case subjects), were compared with 742 boys (median age, 21.0 months) who did not have a UTI (control subjects). The proportion of case and control subjects who were circumcised in each group was compared with the use of the chi-square test, with the strength of association between circumcision and UTI expressed in terms of an odds ratio. To determine whether age was a confounder or an effect-modifier, we stratified the groups by age (<1 year; ≥1 year) and analyzed by the method of Mantel-Haenszel. Results: Of the 144 preschool boys with UTI, 2 (1.4%) were circumcised, compared with 47 (6.3%) of the 742 control subjects (chi-square value = 5.6; p = 0.02; odds ratio, 0.21; 95% confidence intervals, 0.06 to 0.76). There was no evidence that age was a confounder or modified the protective effect of circumcision on the development of UTI (Mantel-Haenszel chi-square value = 6.0; p = 0.01; combined odds ratio, 0.18; 95% confidence intervals, 0.05 to 0.71; Breslow- Day test of homogeneity chi-square value = 0.6; p = 0.4). Conclusions: Circumcision decreases the risk of symptomatic UTI in preschool boys. The protective effect is independent of age.