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Ampicillin and trimethoprim/sulfamethoxazole were shown to be of similar efficacy in the treatment of acute urinary tract infection of children. It was of interest to determine the effects of these antimicrobial drugs on the periurethral flora and recurrence rates. To this end, seventeen girls with twenty-two separate infections of the urinary tract were treated randomly with a ten-day course of either ampicillin or trimethoprim/sulfamethoxazole. Cultures of the urine and periurethral area were obtained before, during (third day), and after (seventeenth day) therapy. All Escherichia coli strains were serotyped. Both treatments resulted in the disappearance of the pathogens from the urine by the third day in all cases, and in all but one patient on the seventeenth day. The causative agents persisted more frequently in the periurethral area than in the urine on both the third and seventeenth days in patients treated with either ampicillin or trimethoprim/sulfamethoxazole. The recurrence rates by the seventeenth day were 50% (4/8) in the ampicillin group, and 14% (2/14) in the trimethoprim/sulfamethoxazole group. Although suggestive in favor of the latter treatment, the difference is not statistically significant. In two of the three re-infections in the ampicillin group the microorganisms causing the second attack were present in the periurethral area on the third day. Sixteen of the seventeen girls were studied radiologically; six (37%) had radiologic abnormalities.