A rabbit model was used to determine the effects of prostaglandins and arachidonic acid on cellular integrity and survival during endotoxic shock. Prostaglandins A2, E1 and F2alpha were infused intravenously at a rate of 1.0 microgram/kg/min for 105 min beginning 15 min after the administration of an LD60 dose of Escherichia coli endotoxin. While each of the prostaglandins tested significantly attenuated the accumulation of lactic acid dehydrogenase in the plasma of shocked animals, none were able to protect against the increase in the plasma activities of glutamic pyruvic transaminase or cathepsin D during the shock state. Prostaglandins A2, E1 and F2alpha did not significantly enhance the survival of the treated animals as compared to vehicle-treated controls. In contrast, arachidonic acid 15 microgram/kg/min i.v.) significantly prevented the accumulation of lactic acid dehydrogenase and glutamic-pyruvic transaminase activities in the plasma of shocked animals, and also significantly increased the number of survivors in this group 48 hours after the endotoxin administration. In summary, while the treatment of endotoxic rabbits with prostaglandins of the A, E and F series was of no survival value, the treatment of these animals with a substrate of the prostaglandin synthetase complex resulted in a dramatic increase in the survival rate. The mechanism of action of arachidonic acid in this regard is not clear.