We have compared the efficacy josamycin (750 mg/12 h/orally) versus penicillin V (500 mg/8 h) for the treatment of acute tonsillitis in a prospective randomized study. Of the 82 eligible patients, 18 were diagnosed of infectious mononucleosis and excluded and the remaining 64 could be evaluated. The duration of the fever and the clinical evolution was similar away the 31 randomized to receive josamycin and the 27 treated with penicillin. In conclusion, josamycin seems to be a useful alternative to penicillin for the treatment of acute tonsillitis.