The ability of antibiotics to penetrate into the respiratory tract has been investigated at several sites, namely, sputum and bronchial secretions, tissue homogenates, pleural fluid and, more recently, epithelial lining fluid and alveolar macrophages. The major reason for such investigations is that these data may be helpful to a more thorough understanding of drug distribution in the lung tissue and fluids and to a more accurate prediction of clinical outcome. However, the study of drug concentration at each of these sites presents problems in terms of methodology and data interpretation. The advantages and disadvantages of each of these methods are considered, and the data on penetration of betalactams, aminoglycosides, macrolides, fluoroquinolones and other antimicrobial agents (including antifungal and antiprotozoan drugs) are reviewed.