Lung metabolism on exposure to hyperbaric oxygen was studied in rat lungs perfused with artificial media and ventilated with O2 at 0.2, 1, or 5 ATA. During the first 80 min of exposure to O2 at 5 ATA, glucose utilization increased 55%, lactate plus pyruvate production increased 45%, total CO2 production increased 47%, tissue ATP decreased 17%, and the ATP/ADP decreased 29% compared with 0.2 ATA O2. The increased CO2 production was due to a nearly twofold stimulation of pentose cycle activity whereas mitochondrial CO2 production did not change significantly. There were no significant differences in metabolism between lungs studied at 0.2 and 1 ATA O2. During the next hour of perfusion, there was a marked increase in mitochondrial CO2 production of control lungs but tissue ATP/ADP did not change significantly. With oxygen at 5 ATA, mitochondrial CO2 production increased only slightly, tissue ATP/ADP decreased further, and lungs demonstrated accumulation of edema fluid. The results indicate that exposure of lungs to hyperbaric oxygen results in stimulation of NADPH turnover through the pentose cycle and increased ATP generation, although the increased rate was not sufficient to maintain normal ATP/ADP.