Langerhans' cells are a defined subpopulation of the mononuclear phagocyte system known to accumulate in the lung in histiocytosis X, an interstitial lung disorder strongly linked to cigarette smoking. To evaluate the hypothesis that cigarette smoking itself may be associated with the accumulation of Langerhans' cells in the lung, normal nonsmokers (n = 5) and normal smokers (n = 10) were evaluated by bronchoalveolar lavage for the presence of Langerhans' cells as identified by the OKT6 monoclonal antibody and by transmission electron microscopy. While the OKT6 antibody identified 0.1 ± 0.1% of the cells recovered from nonsmokers, it labeled 1.1 ± 0.3% of those recovered from smokers (p < 0.01). Furthermore, while electron microscopy demonstrated no Langerhans' cells among the lavage cells from nonsmokers, 0.4 ± 0.1% of the cells recovered from normal smokers contained characteristic intracytoplasmic Birbeck granules, positively identifying them as Langerhans' cells. We conclude that cigarette smoking is associated with an expansion in the population of Langerhans' cells on the epithelial surface of the lower respiratory tract. While the mechanisms underlying this accumulation are unknown, it is possible that the properties of these cells contribute to the derangements of the pulmonary parenchyma found in cigarette smoking and establish a biologic link to the already observed epidemiologic association between histiocytosis X and cigarette smoking.