3,4-methylenedioxymethamphetamine (MDMA), a substituted amphetamine analogue which stimulates serotonin release in the CNS, has been shown to induce near lethal elevations in core temperature in the rat. To characterize the effects of MDMA on temperature regulation, the study measured metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), and colonic temperature (Tc) in male, Long-Evans rats at 60 min following 30 mg/kg (s.c.) MDMA or saline at ambient temperatures (Ta) of 10, 20, and 30C. MDMA caused an elevation in MR at Ta's of 20 and 30C but had no effect at 10C. At a Ta of 30C, MR of the MDMA group was double that of the saline group. EWL was elevated by MDMA, an effect which was potentiated with increasing Ta. MDMA also elicited an increase in MA at all three Ta's. MDMA led to a 3.2C increase in Tc at 30C, no change in Tc at 20C, and a 2.0C decrease in Tc at 10C. The data suggest that, at relatively warm Ta's, MDMA-induced stimulation of serotonergic pathways causes an elevation in MR and peripheral vasoconstriction, thus producing life-threatening elevations in Tc. The increase in EWL following MDMA partially attenuates the hyperthermia at warm Ta's and leads to hypothermia in the rat maintained at a cold Ta of 10C.