Abstract Hyperthermia has been implicated as a contributing factor in the toxicity of amphetamine in aggregated mice. Acute exposure of mice to simulated altitude (ALT), an environmental stress which lowers body temperature, also increases amphetamine lethality. Thermal responses to amphetamine were obtained at ALT to determine whether elevated body temperatures would be similarly related to the lethal effects of this drug. Accordingly, rectal temperatures (Tr) after ip administration of d-amphetamine SO 4 were monitored continally for 4 hours in isolated mice at sea level (SL) and an ALT of 19,000 feet. At SL, all doses of amphetamine resulted in hyperthermia; lethality occurred only with 75, 100, and 125 mg/kg, with no fatalities at 10, 25, 40, and 60 mg/kg. At ALT, Tr of control mice were reduced 5°C within 1 hour. Increased lethality with amphetamine at ALT was apparent between 25 and 75 mg/kg, while hypothermia was present at all dose levels although not as marked as the controls. Hypothermia at ALT was least evident with 10 mg/kg (2.5°C in 1 hour), a dose which had minimal effects on lethality. It would appear, therefore, that the hyperthermic effects of amphetamine were not associated with the increased lethality at altitude.