To determine possible characteristic changes of alveolar macrophages, we used light and electron microscopy to study 25 lung biopsy specimens from patients who had received respiratory therapy or from chronic inhalative smokers. In addition to investigating the density and size of the alveolar macrophages and the number and size of their inclusion bodies, we also performed a histochemical analysis of these cells. In lungs of chronic smokers and of patients who had received respiratory therapy for adult respiratory distress syndrome, the number of alveolar macrophages was 8-10 fold above normal. The macrophages differed in size and shape and were characterized by a variety of heterogeneous inclusions. However, a comparative analysis of the alveolar macrophages showed no significant differences in density, cell diameter, or number and size of the inclusion bodies. In some so-called smokers' macrophages, crystalline inclusion bodies could be demonstrated, probably kaolinite. Fifteen morphologically different inclusion bodies were observed in alveolar macrophages. With the exception of inclusions characteristic of lipid phagocytosis, e.g., myelin structures, erythrocytes, and kaolinite crystals, there was no correlation between the ultrastructure of the storage granules and the phagocytized material. These findings indicate that the activation of the alveolar macrophages of the lung is an unspecific reaction to exogeneous (cigarette smoke) and endogenous (accumulation of cell detritus or fibrin) stimulation. Organic substances are degraded to amorphous, sometimes lipophilic structures. The presence of anorganic foreign bodies like kaolinite crystals permits histochemical and histophysical conclusions about the phagocytized material which can not be decomposed in the lysosomes.(ABSTRACT TRUNCATED AT 250 WORDS)