The efficacy of trimethoprim (TMP) as a single therapeutic agent in the treatment of urinary tract infection (UTI) in children was studied in 112 children prospectively comparing TMP against trimethoprim-sulfamethoxazole (TMP/Sulfa), sulfamethoxazole and ampicillin. Children with repeated colony counts of greater than 100,000 CFU/ml of the same organism grown in 2-3 consecutive clean catch specimens were successively assigned to each treatment group for 10 days' therapy. TMP achieved a cure rate of 100% compared to TMP/Sulfa 100% (p greater than 0.05), sulfamethoxazole 93% (p less than 0.05) and ampicillin 63% (p less than 0.01). TMP and TMP/Sulfa groups had no failures while sulfamethoxazole and ampicillin groups had 7% (p less than 0.05) and 37% (p less than 0.01), respectively. Relapses occurred in 4% of the TMP group whereas TMP/Sulfa had 7% (p greater than 0.05); sulfamethoxazole and ampicillin groups had none. TMP group had 7% recurrence compared to 6% TMP/Sulfa, 4% sulfamethoxazole and 7% ampicillin (p greater than 0.05). Gastrointestinal side effects and skin rashes were not encountered in the TMP group; depression of WBC was the lowest in this group. As a single therapeutic agent, TMP appears to be safe and efficacious for treatment of acute UTI in children.