The expression of HLA class II genes is essential to the antigen-presenting function of monocytes and macrophages. With a new cytofluorometric method of single-cell analysis we investigated the density of HLA-DR antigen expression on alveolar macrophages (AM) of smokers. Although all AM of nonsmokers (100 +/- 1%) expressed HLA-DR antigens, only 79 +/- 12% of AM from smokers showed positive findings (p less than 0.001). Furthermore, the antigen density of those cells expressing this antigen was significantly reduced in smokers (p less than 0.001). The defective expression of class II genes on AM of smokers might contribute to the impaired antigen-presenting function found by some previous investigators.