To investigate the influence of cigarette smoking on alveolar macrophages (AM) we compared morphologic and immunocytochemic characteristics of bronchoalveolar lavage cells collected from 10 smokers and 8 nonsmokers. AM were studied using single cell fluorescence photometry. AM of smokers were larger in size (p < 0.001), showed stronger autofluorescence (p < 0.001), and expressed fewer HLA-DR antigens (p < 0.001) compared with AM of nonsmokers. AM of smokers were more heterogeneous in respect to cell size, autofluorescence, and HLA-DR antigen expression. HLA-DR antigen density on AM of smokers was independent of cell size and autofluorescence. This suggests that tobacco smoke reduces HLA-DR antigen expression in AM of different maturational states and that this defective expression of HLA class II antigens is not dependent on the amount of phagocytosed autofluorescent tobacco particles.