OBJECTIVE To compare the efficacy and tolerability of a 3-day course of azithromycin with a 10-day course of amoxicillin/clavulanic acid in the treatment of acute sinusitis in adults. METHODS One hundred adult patients with acute sinusitis were included in an open, randomized study. Clinical diagnosis of sinusitis was confirmed by nasal endoscopy, sinus radiography, and (when possible) by culture of sinus aspirate. Patients were randomized to receive azithromycin (500 mg once daily for 3 days) or amoxicillin/clavulanate (625 mg every 8 hours for 10 days). RESULTS A significantly faster resolution of signs and symptoms of sinusitis was observed in the azithromycin-treated patients. By the end of therapy (days 10-12), 95% of the patients in the azithromycin group and 74% in the amoxicillin/clavulanate group were cured. The remaining patients' conditions were improved. By the follow-up visit, cure was achieved in 98% of the azithromycin-treated patients, and 91% of the amoxicillin/clavulanate-treated patients. Treatment failure was observed in three patients from the amoxicillin/clavulanate group, and relapse occurred in one patient from each group. Bacteriologic eradication was achieved in 23 of 23 and 21 of 24 patients treated with azithromycin and amoxicillin/clavulanate, respectively. Both drugs were well tolerated. Two patients (4%) from the azithromycin group and five patients (10%) from the amoxicillin/clavulanate group reported mild gastrointestinal disturbances. CONCLUSIONS In adults with acute sinusitis, a 3-day course of azithromycin was as effective and well tolerated as a 10-day course of amoxicillin/clavulanic acid. A significantly simpler dosage regimen and faster clinical effect were the advantages of azithromycin.