Thirty-six girls, aged two to 17 years, with culture-proven, acute, uncomplicated lower urinary tract infections and without signs or symptoms of upper urinary tract infection, were randomized to receive either single-dose amoxicillin or conventional therapy for ten days. Twenty-six patients completed the study, ten in the single-dose group and 16 in the conventional therapy group. The patients treated with single-dose therapy had cure rates (70% vs 75%), relapse rates (30% vs 25%), and reinfection rates (0% vs 12%) comparable to those of conventionally treated patients. A significant difference in the induction of resistant organisms was seen between treatment groups (P less than .05). All single-dose relapses were due to failure to clear a sensitive organism from the urinary tract. All relapses on conventional therapy resulted from an initially sensitive organism becoming resistant to amoxicillin during treatment. Single-dose antibiotic therapy of uncomplicated urinary tract infections in children is effective in patients with culture-proven infections selected by clinical criteria, and appears to be safe when combined with conscientious long-term follow up and radiographic evaluation. Single-dose therapy offers the advantage of selecting significantly fewer resistant organisms from the gut flora than do conventional antibiotic regimens.