Adults with mild to moderate community-acquired pneumonia were treated with azithromycin (500 mg once daily for 3 days) or clarithromycin (250 mg twice daily for 10 days) and clinically assessed between days 3 and 7 and days 12 and 16. Patients classified as improved at the day 12-16 visit were also evaluated between days 19 and 23. Two hundred three patients were treated (101 with azithromycin, 102 with clarithromycin). A satisfactory clinical response was recorded at the end of therapy in 83 of 88 (94%) evaluable azithromycin-treated and 84 of 88 (95%) evaluable clarithromycin-treated patients (P=0.518). At day 19-23, only one patient in each treatment group had relapsed. Thirty-one of 32 (97%) pathogens isolated from patients in the azithromycin group were eradicated, compared with 32 of 35 (91%) isolated from clarithromycin patients. In all patients with atypical pneumonia, the clinical response was satisfactory at follow-up. Incidences of treatment-related adverse events were similar for the two groups (P=0.815). Two (2%) clarithromycin patients discontinued therapy due to severe treatment-related adverse events; none in the azithromycin group did. This study shows that a 3-day, once-daily course of azithromycin is as clinically effective and well tolerated as a 10-day, twice-daily course of clarithromycin in the treatment of mild to moderate community-acquired pneumonia.