It is well documented that caffeine exacerbates the hyperthermia associated with acute exposure to 3,4-methylenedioxymethamphetamine (MDMA) in rats. Previous reports have also indicated that MDMA-related enhancement of dopamine release is exacerbated in the presence of caffeine. In the present study we have examined whether the effects of MDMA on real-time stimulated dopamine release in the absence of uptake inhibition are accentuated in the presence of caffeine. Isolated striatal slices from adult male Wistar rats were treated acutely with MDMA, caffeine, or a combination, and their effects on single and 5 pulse stimulated dopamine release monitored using the technique of fast cyclic voltammetry. Caffeine at 10 or 100μM had no significant effect on single pulse stimulated dopamine release. However 100μM caffeine caused a significant peak increase in 5 pulse stimulated dopamine release. Both 1 and 30μM MDMA gave rise to a significant increase in both single and 5-pulse dopamine release and reuptake. A combination of 100 μM caffeine and 1 or 30μM MDMA did not significantly enhance the effects of MDMA on single or 5 pulse dopamine release and reuptake when compared to that applied alone. Utilizing single action potential dependent dopamine release, these results do not demonstrate a caffeine-enhanced MDMA-induced dopamine release.