Bronchial epithelial damage and mucus hypersecretion are characteristic features of chronic airway inflammation that can impair mucociliary clearance and can cause recurrent or persistent respiratory infection. In response to chemoattractants produced by damaged or inflamed tissue, neutrophils move through sequential steps of recruitment, migration, accumulation, and adhesion to endothelial and bronchial epithelial cells. Neutrophils engage in bacteriocidal activity by phagocytosis, release of lysosomal enzymes, and generation of reactive oxygen species, and they synthesize and release proinflammatory cytokines. Data confirm that many macrolide antibiotics have nonbactericidal properties that include inhibiting inflammatory cell chemotaxis, cytokine synthesis, adhesion molecule expression, and reactive oxygen species production. Macrolides also can decrease airway mucus hypersecretion in patients with diffuse panbronchiolitis, chronic sinusitis, and chronic bronchitis. Macrolides accumulate in neutrophils and macrophages at significantly higher concentrations than in extracellular fluid. This article discusses the action of macrolides on neutrophil accumulation, immune complex-mediated production of nitric oxide, mucin production, and the expanded therapeutic role of macrolides as biological response modifiers.