Since dirithromycin persists at high concentrations in the lung for at least 3 days following the last dose of a 5-day course, we evaluated the clinical efficacy and tolerance of a 5-day course of dirithromycin in 20 patients with acute exacerbation of severe chronic obstructive pulmonary disease, treated with a total dose of 2.5 g dirithromycin (500 mg once-daily for 5 days) in an open, non-comparative study. Patients were assessed before therapy and after 5 (last administration), 10 (post-therapy) and 20 (late post-therapy) days. Pathogen elimination or presumed elimination was seen in 18/20 patients at the post-therapy visit and at the late post-therapy visit, but two Haemophilus influenzae out 5 were isolated in sputum after 10 days and only one after 20 days (Pseudomonas aeruginosa was the other pathogen). Dirithromycin was well-tolerated and only 2 patients reported mild gastrointestinal pain. This study shows that a 5-day dirithromycin therapy provides a convenient and efficient dosage regimen in acute exacerbation of chronic bronchitis. Notwithstanding its poor in vitro activity against H. influenzae, dirithromycin was fairly active against this microorganism in vivo.