Poor cognitive performance in ecstasy (3,4-methylenedioxymethamphetamine; MDMA) users has been related to the well-recognized neurotoxic effects of the drug upon central serotonergic and possibly also dopaminergic systems. However, concomitant use of other drugs has been a critical confound in most investigations. In this study we used an n-back task and fMRI to investigate working memory performance and related cerebral activation in eight, currently abstinent pure MDMA users and two matched groups of polyvalent MDMA users and non-users. Pure MDMA users presented lower activations than controls and/or polyvalent users, most notably in inferior temporal regions, the angular gyrus and the striate cortex, whereas polyvalent users did not differ from controls. Our results suggest that altered brain activation patterns during cognitive processing in ecstasy users may be mainly associated with prior MDMA use. Concomitant use of other drugs may modify this effect.