Seventy-eight patients participated in this multicenter, third-party-blinded study comparing a single daily dose of azithromycin for 5 days (500 mg on day 1 followed by 250 mg/day for days 2-5) with amoxicillin (500 mg three times daily) for 10 days in the treatment of acute bacterial maxillary sinusitis. A total of 38 evaluable patients contributed to the efficacy analysis. The overall clinical response rate was 100% for both antibiotics. The clinical cure rate, as determined by the investigator, was 73.9% for azithromycin and 73.3% for amoxicillin; improvement was seen in 26.1% and 26.7% of patients, respectively. The bacteriologic cure rate in these 38 patients was 100% in both groups. Both antibiotics were well tolerated; side effects were reported by 4.9% of patients in the azithromycin group compared with 8.1% in the amoxicillin group. Most of these side effects were gastrointestinal disturbances that were reported by four of five (three amoxicillin, one azithromycin) patients experiencing side effects. All side effects were mild, and in both groups only minor abnormalities in laboratory data were detected. No patient discontinued the study because of treatment-related side effects. In this study, a 5-day course (one dose per day) of azithromycin proved to have efficacy, safety, and tolerability that was equal to a 10-day course (three doses per day) of amoxicillin in the treatment of acute bacterial sinusitis.