To determine the effectiveness of a short (five-day) course of penicillin V potassium therapy, 172 patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis were randomly assigned to receive 250 mg of penicillin V potassium three times daily for either five or ten days. The patients in the two treatment groups were comparable with respect to clinical findings, compliance, and serologic response to GABHS. A bacteriologic treatment failure was defined as the presence of the same serotype of GABHS in the follow-up as in the initial throat culture and occurred in 13 (18%) of the 73 patients in the five-day treatment group and in six (6%) of the 99 patients in the ten-day treatment group. These findings support the current recommendation for a full ten days of oral penicillin V therapy for the treatment of GABHS pharyngitis.