(+)-3,4-Methylenedioxymethamphetamine (MDMA;'Ecstasy') is a ring substituted phenylisopropylamine that is structurally related to both amphetamines and hallucinogens. The unique behavioural activating properties of MDMA have led to its widespread abuse. MDMA induces many neurochemical, behavioural and endocrine alterations which closely resemble those elicited by exposure to acute stress, suggesting that MDMA could be regarded as a 'chemical stressor'. In addition to the neurochemical, behavioural and endocrine effects of stressor exposure, it has been reported that stress produces alterations in immune function. However, to date the effects of MDMA on immune function have been restricted to in vitro investigations. In this study we report, for the first time, that acute in vivo administration of MDMA (20 mg/kg, i.p.) produced a rapid (within 30 min) suppression of Con A-induced lymphocyte proliferation and a profound reduction in the total leucocyte count in rats that persisted for at least 6 h following injection. These alterations in immune function were accompanied by a significant increase in plasma corticosterone concentrations 30 min post MDMA administration which had returned to baseline values within 6 h of drug administration. In addition, there was a significant depletion in cortical 5-HT concentrations both 30 min and 6 h after MDMA administration. The results of this study provide evidence that in addition to the well established toxic effects of MDMA on the central serotonergic system, a single administration of this widely abused drug induces a rapid and sustained suppression of immune function.