An investigation was performed to compare the effectiveness of oral penicillin V given twice daily with penicillin V given three times daily in the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis. Patients were randomly assigned to receive 250 mg of penicillin V either two or three times daily for ten days. Overall, 23 (23%) of 99 patients had the same strain of GABHS isolated from their follow-up as from their initial throat culture and were considered to have bacteriologic-treatment failures. Of the 50 patients in the three-times-daily group, nine (18%) had bacteriologic-treatment failures, while 14 (28.5%) of 49 patients in the twice-daily group had bacteriologic-treatment failures. The results of this and earlier investigations suggest that penicillin V given twice daily is as effective as penicillin V given three times daily for the treatment of GABHS pharyngitis.