A B S T R A C T Human alveolar macrophages were lavaged from surgically resected lungs and from lungs of normal subjects. Macrophages that had been purified by glass adherence were maintained in tissue culture for as long as 54 days. After 3-4 wk in vitro they underwent transformation into multinucleated giant cells. These aged cells had more than 30 times the phagocytic capacity that the same group of cells had had after 1 day in vitro.Phagocytosis of heat-killed Candida albicans was inhibited by iodoacetate, sodium fluoride, potassium cyanide, and low partial pressures of oxygen, suggesting that these cells require both oxidative and glycolytic energy sources for maximal particle ingestion. Alveolar macrophages and monocyte-derived macrophages killed Listeria monocytogenes with similar efficiency, but neutrophils were more efficient than either of the other cell types. Bacterial killing is probably not dependent upon myeloperoxidase in the monocyte-derived macrophage or in the alveolar macrophage since histochemical stains for peroxidase do not stain either cell type. C. albicans blastospores, which are killed by neutrophils and monocytes that contain myeloperoxidase, were not killed by human alveolar macrophages during the 4 hr of observation.Large cells with supernormal phagocytic capacity were recovered from patients with postobstructive pheumonia and from one patient with recurrent bacterial pneumonia, indicating that macrophage function can be altered in certain disease states.Human alveolar macrophages are unique human phagocytes in their dependence on an oxygen tension greater than 25 mm HG for maximal phagocytosis. Carbon dioxide tensions as high as 70 mm Hg did not alter phago-