To evaluate the effect of cigarette smoking on the number, distribution, and differentiated state of dendritic cells (DC) and Langerhans cells (LC) in the human lung, we have quantitated the number of these cells present in the bronchioles and alveolar parenchyma of lung tissue from nonsmokers and cigarette smokers using anti-CD1 monoclonal antibodies which react preferentially with DC (M241) and LC (T6). M241+ DC were found in the bronchiolar submucosa and alveolar parenchyma of nonsmokers; T6+ LC were present within the bronchiolar epithelium. Cigarette smoking was associated with a twofold increase in the total number of cells of DC/LC lineage and a 30-fold increase in the number of T6+ cells, many of which contained Birbeck granules (LC), present in the alveolar parenchyma. Most LC found in the parenchyma of smokers were observed in close association with areas of alveolar type II pneumocyte hyperplasia. Cigarette smoking did not change the number of differentiated state of cells of DC/LC lineage within the bronchioles. Both DC and LC are present in the human lung. Cigarette smoking has an important effect on the number, distribution, and differentiated state of these cells, which may explain why most adult patients who develop Langerhans cell granulomatosis are smokers.