In a randomized, prospective, multicenter study the clinical and bacteriological efficacies of three dosage schedules with two different salts of oral penicillin V suspensions (regimen 1: potassium salt of penicillin V, 50,000 U/kg of body weight per day in three divided doses; regimen 2: benzathine salt of penicillin V, 50,000 U/kg of body weight per day in two divided doses; and regimen 3: benzathine salt of penicillin V, 100,000 U/kg of body weight in two divided doses) for the treatment of streptococcal pharyngitis were evaluated. Children with clinical signs of acute pharyngitis and a positive throat culture for group A beta-hemolytic streptococci (GABHS) were eligible. There was no difference between the treatment groups with respect to the overall clinical success rate. Eradication of the original serotype of GABHS from throat cultures was achieved in 87.1% (regimen 1), 85.5% (regimen 2) and 87.7% (regimen 3) of patients. The incidence of potential drug-related adverse events was significantly higher in patients treated with regimen 3. The results of this and earlier studies strongly suggest that oral penicillin given twice daily should be the recommended treatment for the initial treatment of pharyngitis due to GABHS. Doubling the total daily dose is not beneficial in the usual clinical setting. Because of its favorable pharmacokinetics, the benzathine salt of penicillin V appears to be well suited for a twice-a-day dosage schedule.