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, we 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 (SC) MDMA or saline at ambient temperature (Ta) of 10, 20 and 30 degrees C. MDMA caused an elevation in MR at Ta's of 20 and 30 degrees C but had no effect at 10 degrees C. At a Ta of 30 degrees C, 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 3.2 degrees C increase in Tc at 30 degrees C, no change in Tc at 20 degrees C, and a 2.0 degrees C decrease in Tc at 10 degrees C. A second study found that treatment with 20 mg/kg MDMA failed to elicit an increase in blood flow to the tail in spite of a hyperthermic core temperature of 41.4 degrees C. Preliminary studies using radiotelemetry methodology suggested that MDMA lethality is preceded by precipitous elevations in heart rate and core temperature. 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.(ABSTRACT TRUNCATED AT 250 WORDS)