A new macrolide drug, clarithromycin (Biaxin) was compared with amoxicillin/clavulanate (Augmentin) in a single-blind (investigator-blind), randomized, multicenter study of 497 outpatients with acute maxillary sinusitis; treatment was 500 mg clarithromycin bid (n = 246) or 500 mg amoxicillin/clavulanate tid (n = 251). Pathogens included Streptococcus pneumoniae in 22% of patients, Staphylococcus aureus in 16%, Haemophilus influenzae in 10%, and Moraxella catarrhalis in 7%. For evaluable patients, clinical success (cure or improvement) was noted for 97% (128/132) of clarithromycin recipients and 93% (119/128) amoxicillin/clavulanate recipients. Clinically significant improvement in signs and symptoms was comparable between groups. Bacteriologic cure rates were 87% (115/132) and 90% (115/128), respectively. Respective pathogen eradication rates were 87% (125/143) and 90% (125/139). Adverse events not due to concurrent conditions occurred in 41% of the former and 46% of the latter group; most were mild to moderate gastrointestinal upsets (21% and 38%, respectively; P < 0.001). We conclude that clarithromycin appears to be as effective as amoxicillin/clavulanate in acute maxillary sinusitis and may cause fewer gastrointestinal upsets.