Alveolar macrophages were prepared from 15 healthy elderly male current smokers 60.9 +/- 9.9 yr of age (mean +/- SD). Alveolar macrophages from 11 elderly male nonsmokers 66.7 +/- 8.1 yr of age served as controls. Production of oxygen radical species was higher in alveolar macrophages from current smokers than in those from nonsmokers in the presence and absence of phorbol myristate acetate (29.8 +/- 15.5 versus 13.7 +/- 8.2 mumol/10(6) cells and 3.8 +/- 1.6 versus 2.2 +/- 1.2 mumol/10(6) cells, respectively, p < 0.01). Decreases in antioxidant activity were observed in cells from smokers versus those from nonsmokers for Cu, Zn-superoxide dismutase (114 +/- 41 versus 210 +/- 73 units/mg protein, respectively, p < 0.01), glutathione S-transferase (0.217 +/- 0.091 versus 0.368 +/- 0.017 units/mg protein, p < 0.01), and glutathione peroxidase (0.736 +/- 0.779 versus 1.590 +/- 0.879 units/mg protein, p < 0.05). Immunologic estimation showed a decrease in the levels of Cu, Zn-superoxide dismutase in cells from smokers (104.3 +/- 46.4 versus 184.1 +/- 64.4 ng enzyme/mg protein, respectively, p < 0.01). Northern blot analysis of Cu, Zn-superoxide dismutase mRNA showed no apparent difference between the two groups, suggesting not the inactivation of this enzyme but a reduction of the translational step or increased proteolysis. The oxidant and antioxidant imbalance observed in elderly male current smokers may be a factor in the pathogenesis of respiratory tissue injury caused by smoking.