Reactive oxygen species (ROS) are ubiquitous compounds produced by phagocytes with important roles in both host defense and pulmonary inflammation. Enhanced ROS metabolism by alveolar macrophages (AM) has been previously demonstrated in various interstitial lung diseases including sarcoidosis. We studied 17 healthy, nonsmoking volunteers and 10 patients with sarcoidosis by bronchoalveolar lavage, and separated AM on discontinuous Percoll gradients to determine patterns of airspace cell recovery and the corresponding ROS metabolism of density-defined AM subpopulations. AM subpopulations were largely purified from contaminating granulocytes, thereby allowing more accurate estimation of ROS metabolism by AM. In bronchoalveolar lavage material from sarcoidosis patients, increased recovery of cells of high (1.075 gm/ml) density was found, which contrasted with the pattern seen in the volunteers in whom cells of lowest density (1.045 gm/ml) predominated. In addition, dense cells from sarcoidosis patients exhibited enhanced stimulated ROS metabolism compared with cells of similar density obtained from the volunteers or with sarcoid cells of lower density. At least three mechanisms may contribute to increased lung oxidative burden in sarcoidosis. The combination of increased bronchoalveolar lavage cell counts, increased cell recovery at high density, and increased cell function produced substantial increases in the total oxidative burden imposed on the lungs of sarcoidosis patients by airspace cells. We conclude that AM metabolism of ROS is dependent on the density and, by implication, the maturity of the cells and that regulation of AM ROS metabolism differs markedly between sarcoidosis patients and healthy volunteers.