This research assessed the effects of a demonstrably neurotoxic dose regimen of MDMA on cognitive function, including learning and memory, in rhesus monkeys. Three of six adult rhesus monkeys received 10 mg/kg MDMA daily for four consecutive days, and three vehicle-treated monkeys served as controls. 13 months after MDMA or vehicle, monkeys were assessed on a test battery specifically designed to assess cognitive function in monkeys. The test battery included measures of working memory (self-ordered spatial search), sustained attention in goal-directed behavior (progressive ratio reinforcement), reaction time (RT) and bimanual dexterity (removing raisins from a transparent plastic board with holes). Concentrations of serotonin and its metabolite 5HIAA were measured in cerebrospinal fluid (CSF) collected under ketamine anesthesia at 9, 13 and 16 months after MDMA or vehicle. Brain serotonin and 5HIAA were assessed directly in 2 MDMA-treated monkeys and two controls killed 17 months after MDMA (one month after cognitive assessment), and in one MDMA-treated monkey killed 20 months post-MDMA. At baseline, before pharmacological challenge, task performance by MDMA-treated monkeys did not differ from controls, and the two groups performed similarly after challenge with the 5HT2A antagonist ketanserin and the 5HT1A agonist 8-hydroxy-aminotetralin (8-OH-DPAT). However, MDMA-treated animals showed greater sensitivity to the RT-slowing and progressive ratio reducing actions of challenge with mCPP (m-chlorophenylpiperazine) than controls. While analysis of CSF failed to find reduced 5HIAA in MDMA-treated monkeys, a 76% to 93% reduction in brain serotonin was found in all cortical areas (frontal, parietal, temporal and occipital) in MDMA-treated monkeys. However, no reductions in serotonin or 5HIAA were seen in sub-cortical areas after MDMA. As has been reported in other studies (e.g. Winsaur et al. 2002; Frederick et al. 1998), the researchers for the most part failed to find any impairments in cognitive function after neurotoxic dose regimen of MDMA in monkeys. It is difficult to reconcile findings reported here with findings of impaired memory and executive function in ecstasy users. Study findings suggest that assessment of cognitive function may not prove to be a good gauge of serotonin neurotoxicity in primates, and that behavioral effects of neurotoxic doses of MDMA are subtle in non-human primates.