Amoxicillin, a new semisynthetic penicillin, was compared with ampicillin in the treatment of otitis media. Pediatric patients from a private practice underwent aspiration of the middle ear for culture. Sixty-seven patients were treated with either amoxicillin three times a day or with ampicillin four times a day. The dose of ampicillin was approximately twice the dose of amoxicillin. Only one. of 48 amoxicillin-treated and one of 19 ampicillin-treated patients failed to respond. Amoxicillin was well tolerated, with a single patient developing eosinophilia. None of the patients treated with amoxicillin developed a rash, while one treated with ampicillin did. Amoxicillin administered three times a day is an effective program for the treatment of bacterial otitis media.