The effect of temperature, either along or in combination with pentobarbital or phenytoin, on survival time in the hypoxic (Flo2 = 0.05) mouse was examined. With hypothermia alone only a mild level (35 C) was needed to increase survival time significantly (63%). Between 29 and 40 C, hypothermia alone increased hypoxic survival time and hyperthermia decreased it. When mild hypothermia was combined with moderate doses of pentobarbital or phenytoin, survival time was generally further increased, whereas at lower temperatures or increased drug doses the effect on survival time of combined treatments was unpredictable. In addition, the magnitude of the effect of hypothermia was quite different following injection of pentobarbital and following injection of phenytoin. The practical corollary of these results is that to obtain reproducible results with this model, the temperature of the mice should not vary more than +/- 0.2 to 0.3 C.