Superoxide anion (O2) release by alveolar macrophages (AM) from young asymptomatic cigarette smokers was greater than that by AM from age-matched nonsmokers. Greater O2 release by AM from cigarette smokers was observed before and after stimulation by bacteria or phorbol myristate acetate (PMA). In contrast, oxygen uptake and glucose (1(-14)C) oxidation by unstimulated or stimulated AM from cigarette smokers was the same as that by AM from non-smokers. The selective increase of O2 release by AM from cigarette smokers was not due to a lack of O2 scavenging agent within the cells, since intracellular superoxide dismutase (SOD) was increased in AM from smokers. The potential importance of enhanced O2 release by AM from cigarette smokers was confirmed by demonstrating that lysis of fibroblasts induced by AM from smokers was completely prevented by addition of SOD and catalase.