(1) We have investigated the ability of the 5HT2 -receptor antagonist ketanserin to affect the hyperthermia produced by methylenedioxymethamphetamine (MDMA) in conscious mice and examined whether α1 -adrenoceptor antagonist actions are involved. (2) Mice were implanted with intra-abdominal temperature probes under anaesthesia and allowed 2 weeks recovery. MDMA (20 mg kg(-1) ) was administered subcutaneously 30 min after vehicle or test antagonist and effects on body temperature monitored by telemetry. (3) Following vehicle, MDMA produced a slowly developing hyperthermia, reaching a maximum increase of 1.24 °C at 150 min postinjection. Ketanserin (0.5 mg kg(-1) ) revealed a significant and marked early hypothermia to MDMA, an effect that is mimicked by the α1 -adrenoceptor antagonist prazosin (0.1 mg kg(-1) ). (4) Functional studies revealed antagonist actions of ketanserin at α1 -adrenoceptors in rat aorta and rat vas deferens in vitro indicative of α1 -adrenoceptor antagonist actions at the concentration used in vivo. (5) In conclusion, ketanserin (0.5 mg kg(-1) ) modulates the hyperthermic actions of MDMA in mice. Although we cannot rule out additional actions at 5HT2 -receptors, the actions of ketanserin are consistent with α1 -adrenoceptor antagonism. There is no clear evidence from this study that 5HT2-receptors mediate the hyperthermic response to MDMA.