This study evaluated the safety and efficacy of clarithromycin in the treatment of patients with Group A beta-hemolytic streptococcal pharyngitis. Subjects were treated with either 250 mg clarithromycin twice daily or 250 mg penicillin V four times a day for 10 days and followed for approximately three weeks post-treatment. At the completion of therapy, 96% (45/47) of patients treated with clarithromycin and 89% (43/48) of patients treated with penicillin V were clinically cured or improved. Recurrence of symptoms occurred in 7 and 5 patients who were treated with clarithromycin and penicillin V respectively. Initial bacteriologic eradication was observed in all but one patient. Recurrence of Streptococcus pyogenes occurred in 5 (11%) patients who received clarithromycin and 7 (15%) patients who received penicillin V. The majority of adverse events reported during this study were mild and involved the gastrointestinal tract. Diarrhea was more frequent in patients who received clarithromycin. In this multicenter, randomized, double-blind trial, clarithromycin was as safe and effective as penicillin V in the treatment of Streptococcus pyogenes throat infections.