Pulmonary Langerhans cell granulomatosis (LCG), also called histiocytosis X, is a disorder of unknown etiology characterized by the presence of destructive granulomas containing numerous Langerhans cells (LCs). The process may be localized or multifocal, and it remains unclear whether the same pathogenic mechanism is involved in all forms of the disease. It is often assumed that the massive accumulation of LCs at the sites of the lesions results from the abnormal proliferation of these cells, although it has been suggested that LCG in adults, at least in the lung, could be a reactive disorder initiated by activated LCs. Little is known, however, concerning the mechanisms responsible for the accumulation of large numbers of LCs in the course of the disease, and the relative contribution of recruitment and local proliferation of these cells remains to be established. To investigate this question, the proportion of replicating LCs was evaluated in biopsied granulomas from patients with localized or diffuse form of LCG by means of several histopathological techniques currently used in assessment of cell proliferation. The findings demonstrate that, except for proliferating cell nuclear antigen (PCNA), all parameters measured are low in all forms of the disease. They are similar to those of renewing epithelial cells and clearly less than those of neoplastic cells. These data strongly suggest that LCs in LCG granulomas are not a rapidly dividing cell population and that local LC replication makes only a minimal contribution to granuloma maintenance. Caution appears to be necessary in the use of PCNA as a marker of growth fraction.