The use of pure oxygen atmospheres at reduced pressure in manned spacecraft has stimulated new research interest. Exposure of humans to pure oxygen at total pressures of 5 to 7 psia for up to 30 days has generally produced only subjective and occasional symptomatic distress. Nevertheless, studies with animals have clearly documented toxicity if the exposure to pure oxygen is at higher total pressures. The selection of suitable oxygen atmospheres for manned space flight and the development of protective measures against toxic manifestations will be considerably facilitated by a clearer understanding of the toxic syndrome. Rats, dogs, and monkeys were exposed to pure (98.5%) oxygen at 1 atm and 1/3 atm in a closed, recirculating chamber and in a nonrecirculating chamber. Rats exposed to a pressure of 1 atm showed significant reduction in efficiency of liver mitochondrial oxidative phosphorylation. Weight loss accompanied this change. Insignificant changes were found in liver or lung mitochondrial oxygen consumption; liver or lung NAD, NADH, or NAD/NADH; and arterial blood lactate and pyruvate, and lactate/pyruvate ratio. A composite index of oxygen toxicity was derived from a multivariant data analysis. Exposure of rats to pure oxygen at 1/3 atm showed slight elevation in P/O ratio in 7 days. The ratio returned to normal in 2 weeks and remained so for 8 months. No significant weight changes were observed. Only preliminary experiments with the dogs and monkeys were conducted, therefore no conclusions can as yet be made. There is an indication that monkeys are more resistant to oxygen toxicity at 1 atm than rats.