A total of 251 adults with chronic sinusitis were enrolled into this prospective multicentre, double-blind, double-placebo comparison of ciprofloxacin (500 mg twice daily) with amoxycillin/clavulanic acid (500 mg three times daily). The diagnosis of chronic sinusitis (persistence of clinical symptoms for at least 3 months) was confirmed by computerized tomography scan and/or sinusoscopy prior to therapy. Patients at inclusion had purulent or muco-purulent rhinorrhoea. Staphylococcus aureus (n = 45), Haemophilus influenzae (n = 35), Streptococcus pneumoniae (n = 32) and enterobacteriaceae (n = 31) were isolated from pre-treatment aspirates of the middle meatus. Treatment lasted 9 days, at the end of which nasal discharge disappeared in 71/118 (60.2%) patients of the ciprofloxacin group and 69/123 (56.1%) of those in the amoxycillin/clavulanic acid group. The clinical cure and bacteriological eradication rates were 58.6% versus 51.2% and 88.9% versus 90.5% for ciprofloxacin and amoxycillin/clavulanic acid, respectively. These differences were not significant, however, amongst patients who had a positive initial culture and who were evaluated 40 days after treatment. Ciprofloxacin recipients had a significantly higher cure rate than those treated with amoxycillin/clavulanic acid (83.3% vs. 67.6%, p = 0.043). Clinical tolerance was significantly better with ciprofloxacin (p = 0.012), essentially due to a large number of gastro-intestinal related side-effects in the amoxycillin/clavulanic acid group (n = 35). Ciprofloxacin proved to be at least as effective as amoxycillin/clavulanic acid. The superior safety profile, a twice daily dosage regimen, suggests that ciprofloxacin may be a useful therapeutic alternative for the treatment of chronic sinusitis.