This multicenter, randomized open-label study compared the efficacy and safety of roxithromycin tablets 300 mg once a day (Rx) and amoxicillin/clavulanic acid tablets 875+125 mg twice a day (Acx), administered for a mean of 7 days. The study was carried out in five centers on 100 in- or out-patients of both sexes, aged between 18 and 91 years (mean 38+/-14). All patients suffered from ENT diseases, 85% with acute otitis media, 31% pharyngotonsillitis and 11% rhinosinusitis. The patients were divided into two randomized groups of 50 patients each. Clinical evaluations (signs and symptoms) were performed before, during and at the end of therapy. At the end of therapy, for intent-to-treat and per-protocol populations, a satisfactory overall clinical response was achieved by 82% of patients in the Rx group and 78% in the Acx group with similar reductions in signs and symptoms of disease in both groups. Safety was good, with only 2 patients of the Rx group and 4 patients of the Acx group presenting side effects, involving mainly the gastrointestinal system. Rx appears to be active and safe in the therapy of ENT diseases exhibiting similar effects on the reduction of signs and symptoms as Amx but with better compliance because of once-a-day administration.