Thirty children with urinary tract infection and nonobstructive vesicoureteral reflux have been followed prospectively for a mean of 17 months. After classification according to age and grade of reflux, 10 patients were assigned at random to treatment with antimicrobial prophylaxis alone or antimicrobial prophylaxis plus corrective surgery. Twenty other patients were also treated with antimicrobial prophylaxis alone. All were assigned at random to treatment with a single daily dose of trimethoprim-sulfamethoxazole or nitrofurantoin. Cultures of urine, complete blood cell counts, and determination of levels of aspartate aminotransferase in serum were performed regularly during follow-up. Both drugs proved effective in prevention of recurrent infection, and no significant hematologic or hepatic abnormalities were noted. Current results suggest that either prophylaxis or surgery may effectively prevent chronic pyelonephritis or reflux nephropathy, but only continuing evaluation of this group of patients will confirm these results.