3,4-Methylenedioxymethamphetamine [(MDMA) or ecstasy] is a popular club drug often used in combination with ethanol. In the current study, we investigated the effects of MDMA and ethanol combinations on locomotor activity and body temperature of rats. For four consecutive days, male Long-Evans rats were treated daily with a 10-mg/kg dose of MDMA with or without a 1.5-gikg dose of ethanol. 3,4-Methylenedioxymethamphetamine increased spontaneous activity (on average +1,140%), and this increase was potentiated by ethanol on all days (on average + 1,710%). Moreover, ethanol inhibited the MDMA-induced hyperthermia (on average -1.3 degrees C) by the first day of treatment, but not on subsequent treatment days, supporting the suggestion that this effect may undergo tolerance. These observations seem to indicate that combined ethanol-MDMA may induce effects on locomotor activity and thermoregulation that involve separate mechanisms, the first one being less sensitive to tolerance than the second one might be. Results of our study have important implications for understanding the motivation and the health risks of polydrug abusers combining ecstasy and ethanol. (c) 2005 Elsevier Inc. All rights reserved.