Mild and moderate vesicoureteral reflux is expected to resolve spontaneously in most children treated medically; however, maximum benefit or minimum risk of such therapy has not been defined. A prospective 5-year followup study of infants and children younger than 5 years at entry with primary vesicoureteral reflux (grades I to III/V) and radiographically normal kidneys after the first recognized urinary tract infection was initiated in 1984. A total of 113 patients was entered from 5 centers and 61% of the patients were less than 2 years old. Vesicoureteral reflux was unilateral in 65 cases (58%) and bilateral in 48 (42%). Of the 226 renal units reflux was grade IV in 4 (2%), III in 51 (22%), II in 81 (36%) and I in 25 (11%), and 65 (29%) had no vesicoureteral reflux. Data on 59 patients who have completed the protocol were analyzed for this report. Breakthrough urinary tract infection occurred in 20 patients. Of the 84 ureters with vesicoureteral reflux at diagnosis reflux resolved in 67%, and it was of lower grade in 22%, same grade in 8% and higher grade in 2%. Grade I vesicoureteral reflux resolved in 82%, grade II in 80% and grade III in 46% of the ureters. Resolution was better when vesicoureteral reflux was unilateral left (74%) than unilateral right (46%) or bilateral (60%). Renal scarring occurred, on average, in 10% of the kidneys without known vesicoureteral reflux or exposed only to nondilating (grades I and II) reflux and in 28% of those with dilating (grade III) reflux. Thirteen cases had breakthrough urinary tract infection but only after the scar was noted in 5. We conclude that under good medical management during 5 years of followup, even mild and moderate vesicoureteral reflux can be associated with renal injury.