A total of 132 infants and children with grades III and IV primary vesicoureteral reflux was entered into a prospective trial comparing medical to surgical management. Inclusion criteria were an age not exceeding 10 years and a glomerular filtration rate of at least 70 ml. per minute per 1.73 m.2. Children with significant urinary tract malformations and clinical signs/symptoms of dysfunctional voiding were not accepted into the trial. Medical therapy consisted of continuous low dose antibiotic prophylaxis until vesicoureteral reflux resolved. The type of surgical procedure used for the correction of reflux was left to the discretion of the surgeon. Outcome variables included the appearance or progression of renal lesions, rate of renal growth, recurrence rate of urinary tract infection or pyelonephritis, changes in total kidney glomerular filtration rate, development of hypertension and resolution rate of vesicoureteral reflux. Followup at 6, 18, 36 and 54 months after entry included, in addition to history and physical examination, voiding cystourethrography, excretory urography and a urine culture. Of the patients 68 were allocated to the medical group and 64 to the surgical group. They were stratified for age, sex and preexisting renal scarring. Of the patients 10% were boys, 47% were between 2 and 6 years old at entry, 93% had a history of pyelonephritis, 67% had either scarring or thinning of the parenchyma at entry, 87% had grade IV vesicoureteral reflux in at least 1 unit and 56% had bilateral reflux. There were no significant differences in the frequency distribution of entry characteristics between the patients allocated to either group. New renal scarring developed in 22% of medical and 31% of surgical patients (p <0.4). Growth of kidneys with grade IV vesicoureteral reflux was slightly less than normal in the medical (-0.67±0.15 standard deviation) and surgical (-0.42±0.11 standard deviation) groups (p <0.7). Pyelonephritis occurred in 15 medical patients versus 5 surgical patients (p <0.05). There was no significant change in glomerular filtration rate within each treatment group and no difference in glomerular filtration rate between groups. No patient had hypertension during the followup period. The disappearance rate of vesicoureteral reflux in patients with grade IV reflux was ~8% per year. Of the medical patients 75% still had vesicoureteral reflux after 3 years of observation. Thus, children with moderate degrees of reflux, and particularly those with grade IV reflux, have a high prevalence of renal injury when first seen and neither of the treatment modalities used in this study proved superior to the other in protecting the renal parenchyma from further damage. There was, however, a higher incidence of acute pyelonephritis among patients assigned to medical than among those assigned to surgical treatment. Due to the low disappearance rate of grade IV reflux, only about half of the patients are expected to be free of reflux after 9 years of observation.