SummarySuperoxide dismutase (SOD) and glutathione peroxidase (GPx) key enzymes in alveolar macrophages regulating levels of super-oxide anion and hydrogen peroxide, respectively, were observed to fluctuate in response to FIO2of 50 and 85% for 18 to 90 hr. At the lower oxygen tension, SOD rose two-fold and GPx decreased significantly by 18 hr and throughout the exposure periods compared to a delayed increase in SOD activity which was not sustained beyond 66 hr of exposure and a sustained rise in GPx to an FIO2of 85%. Peritoneal macrophages containing lower SOD activity and greater GPx activity than resident alveolar macrophages upon injection into the circulation resulted in a 10-fold accumulation in the lungs during exposure of animals to FIO2of 85% but not at 50%. This study indicates that brief exposure to FIO2of 85% but not 50% resulted in alterations of the vascular integrity of the lungs resulting in the accumulation of circulating macrophages to the alveolar macrophage pool. The delayed rise in SOD activity and the sustained increase in GPx activity in alveolar macrophages from animals exposed to FIO2of 85% could in part be related to this influx of circulating macrophages with enzymatic characteristics observed for peritoneal macrophages.SpeculationToxic concentrations of oxygen not only affect the metabolism and enzyme responses of resident alveolar macrophages but incite the early influx of circulating macrophages into the lung favoring the accumulation of superoxide anion which could propagate the inflammatory reaction.