SUMMARY: The aim of this study was to evaluate the concentrations of dirithromycin, a new macrolide antibiotic, in bronchial secretions (BS), bronchial mucosa (BM), epithelial lining fluid (ELF) and serum in 25 patients with acute exacerbation of chronic bronchitis after a 5 -day, once-daily, dirithromycin regimen. All patients received dirithromycin, (500 \mathrm{mg}) (two (250 \mathrm{mg}) tablets) given orally once daily at 08.00 fasted, for 5 consecutive days. They were divided into five groups ( (n=5) in each group) according to sampling time (24, 48, 72, 96 and (120 \mathrm{~h}) after the last dose). Mean serum concentrations remained low throughout the study ((0.44 \mu \mathrm{g} / \mathrm{ml}) at (24 \mathrm{~h}, 0.31 \mu \mathrm{g} / \mathrm{ml}) at (48 \mathrm{~h}, 0.33 \mu \mathrm{g} / \mathrm{ml}) at (72 \mathrm{~h}, 0.12 \mu \mathrm{g} / \mathrm{ml}) at (96 \mathrm{~h}) and (0.11 \mu \mathrm{g} / \mathrm{ml}) at (120 \mathrm{~h}), respectively), although they were higher than the MICs for Moraxella catarrhalis for up to (72 \mathrm{~h}) and than that for Streptococcus pneumoniae for up to (120 \mathrm{~h}) after the last dose. By contrast, in all other samples, mean concentrations were higher than the MICs for many relevant respiratory pathogens for at least 3 days, and higher than that for (S). pneumonia and M. catarrhalis for up to (120 \mathrm{~h}) (mean concentrations measured 2.67, 2.15, 1.74, 0.27 and (0.17 \mu g / \mathrm{ml}), respectively, in BS; 2.59, 2.59, 1.96, 0.41 and (0.27 \mu \mathrm{g} / \mathrm{g}), respectively, in BM; 2.21, 2.25, 1.57, 0.22 and (0.15 \mu \mathrm{g} / \mathrm{ml}), respectively, in ELF). These findings demonstrate that dirithromycin is concentrated in each of these potential sites of infection for up to 3 days after a 5 -day course of therapy. Therefore, short-term therapy with dirithromycin may be useful for many respiratory infections.