The metabolism of xenobiotics within lung often leads to toxicity, although certain pulmonary cells are more readily damaged than others. This differential susceptibility can result from cell-specific differences in xenobiotic activation and detoxication. The localization and distribution of xenobiotic-metabolizing enzymes (cytochromes P-450, NADPH-cytochrome P-450 reductase, epoxide hydrolase, glutathione S-transferases, UDP-glucuronosyltransferases, and a sulfotransferase) and of aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity determined immunohistochemically and histochemically, respectively, within lung are discussed. Findings reveal that xenobiotics can be metabolized in situ, albeit to different extents, by bronchial epithelial cells, Clara and ciliated bronchiolar epithelial cells, and type II pneumocytes and other alveolar wall cells and that enzymes and activities are not necessarily induced uniformly among these cells.