Although macrolide antibiotics have now been widely used in the treatment of chronic airway infections including diffuse panbronchiolitis and chronic bronchitis, the mechanism of the efficacy remains uncertain. Because the increased mucus glycoprotein secretion from airway goblet cells may play a significant role in the development of such diseases, to determine the effects of macrolides on airway goblet cell secretion, we studied guinea pig airways by a semiquantitative morphometric method. The goblet cell secretion was assessed in histological sections of the trachea and main bronchi stained with Alcian blue and PAS by determining mucus score, which is inversely related to the magnitude of mucus discharge. Intravenous IL-8 decreased mucus score in a dose-dependent manner and increased the number of neutrophils present in bronchoalveolar lavage fluid. Oral administration of clarithromycin at a daily dose of 1-10 mg/day for 2 weeks dose-dependently inhibited IL-8 (5 mg/ kg)-induced decrease in mucus score, with the maximal inhibition being 54 +/- 11% (p < 0.001) in the trachea and 48 +/- 8% (p < 0.01) in the main bronchi. This effect was accompanied by the inhibition of neutrophil accumulation into bronchoalveolar lavage fluid. Erythromycin produced similar inhibitory effects on IL-8-induced goblet cell secretion and neutrophil accumulation, whereas amoxicillin and cefaclor had no effect. These results suggest that macrolides protect against goblet cell hypersecretion probably through an inhibition of recruitment of neutrophils into the airway mucosa.