Sixty 3- to 14-year-old outpatients with positive streptococcal group A bacterial cultures and clinical signs and symptoms of pharyngitis were treated with a single intramuscular (IM) injection of penicillin G benzathine/penicillin G procaine in a multicenter study. At the first follow-up visit, usually within 48 hours of the injection, 60 children had negative cultures, and the mean body temperature had decreased from 100.2 +/- 1.6 degrees F to 98.5 +/- 0.5 degree F (P less than 0.05). At this time, the investigators rated 77% of the children clinically cured and the remaining 23% improved; major signs and symptoms (sore throat, difficulty swallowing, lethargy, and cervical node enlargement and tenderness) had disappeared in nearly all of the children. Initial injection site pain, noted in only 15% of the children 48 hours later, probably was secondary to the injection and not drug related. Most other adverse reactions (in seven children) also were injection related, were mild or moderate, and required no countermeasures. At the second follow-up visit approximately 10 days after injection, all children were considered clinically and bacteriologically cured. Thus, the combination of IM benzathine and procaine penicillin not only is safe and effective but eliminates compliance concerns.