Objective:To investigate a role of the opiate system during acute hypoxic hypoxia, the effects of naloxone and morphine on hypoxic survival rate were investigated in awake adult mice.Design:Prospective, randomized, animal trial.Setting:University research laboratory.Subjects:Male dd-Y mice (n = 864 in experiment I, n = 144 in experiment II, n = 30 in experiment III).Interventions:The animals were placed in an airtight plastic chamber into which a continuous flow of 8 L/min 5% oxygen-95% nitrogen was passed.Measurements and Main Results:One and 5 mg/kg naloxone had no significant effect on the survival rate of mice subjected to acute hypoxic hypoxia, whereas 10 mg/kg naloxone decreased the survival rate. On the other hand, 2 and 5 mg/kg morphine was shown to have a protective action against acute hypoxic hypoxia. The protective effects of 5 mg/kg morphine against hypoxia was even antagonized by 5 mg/kg naloxone, which did not itself show any significant effect on the survival rate. The oxygen consumption in the morphine-treated (5 mg/kg) mice was significantly (p< .05) lower (87.0% ± 4.6%; mean ± SE) than that in the saline-treated animals.Conclusions:The present study suggests that the endogenous opiate system does not play a significant role on the pathophysiology caused by acute hypoxic hypoxia and that the improved survival of the hypoxic animals by morphine is at least partly attributable to its depressant effect on oxygen consumption.