A total of 118 children between 6 months and 10 years of age with acute urinary tract infection were treated in a random; double-blind manner with 12 mg/kg/day of trimethoprim-sulfamethoxazole (61 patients) or 50 mg/kg/day of sulfamethoxazole (57 patients) for ten days. Mean trimethoprim and sulfamethoxazole susceptibilities of Escherichia coli isolated from these patients were 1.2 and 0.6 microgram/ml, respectively. Mean serum concentrations of trimethoprim and sulfamethoxazole were 1.8 and 62 microgram/ml, respectively, one hour after the dose. Of the children who completed the ten days of prescribed medication, clinical and bacteriological cure was confirmed immediately after treatment for all but one patient in each group. Most patients in each treatment group with recurrent infections had underlying urological abnormalities. Severe hematological, renal, or hepatic toxicity requiring interruption of treatment was not encountered. No advantage of trimethoprim-sulfamethoxazole over sulfamethoxazole alone for acute urinary tract infection was demonstrated.