Self-administration of S-(+)-MDMA, R-(-)-MDMA and racemic (both enantiomers) MDMA was examined in rhesus monkeys who already maintained self-administration of 0.01 mg/kg cocaine. Assessment of test drug self-administration were performed by occasionally substituting cocaine with test drug (MDMA, MDMA enantiomer or methamphetamine), and recording whether self-administration was maintained after substitution. Doses of MDMA used were 0.001, 0.003, 0.01, 0.03, 0.1 and 0.3 mg/kg (racemic and both enantiomers), and these were compared with 0.0001, 0.0003 and 0.001 mg/kg racemic methamphetamine. Self-administration of both enantiomers (and the racemate) were maintained in cocaine-trained monkeys, with self-administration following an "inverted U" function (increased response for drug seen with initial increase in dose, but number of responses for drug declining when dose was higher than that maintaining "peak" response). Maximum number of responses for self-administration was maintained by a lower dose of S-(+)-MDMA (0.03 mg/kg) than R-(-)-MDMA (0.1 mg/kg), though it appears that the dose of racemate that produced maximum self-administration was lower than it was for either enantiomer (0.01 and 0.03 mg/kg). No dose of MDMA (racemic or either enantiomer) maintained as much self-administration as either cocaine or methamphetamine. While the 5HT2A receptor antagonist ketanserin produced a downward shift in dose-effect curve in number of responses for S-(+)-MDMA (making it less attractive), and the 5HT2A antagonist MDL100907 produced a rightward shift in S-(+)-MDMA self-administration (the apex of the inverted U was at a higher dose than seen without the 5HT2A antagonist), neither drug suppressed responding for S-(+)-MDMA. Self-administration of R-(-)-MDMA was completely suppressed by pre-treatment with MDL100907, and ketanserin pre-treatment suppressed responding for all but the highest dose of R-(-)-MDMA. Study findings suggest that the rewarding effects of MDMA (particularly the R-(-) enantiomer) are due in part to activity at the 5HT2A receptor. This is surprising because other drugs thought to act on this receptor (LSD, DOM) are not self-administered by rats or monkeys, and only rarely produce dependence in humans. Methamphetamine maintained higher rates of self-administration than did racemic MDMA, or either enantiomer. Since methamphetamine has a duration of action equal to or longer than that of MDMA, disparities between rates of self-administration between MDMA and methamphetamine cannot be explained by differences in duration of action. Taken together, study findings indicate that monkeys will self-administer both R-(-) and S-(+) MDMA, with peak response maintained by slightly lower doses of the S-(+) enantiomer. In addition, finding suggest that activity at 5HT2A receptors are at least partly involved in producing the rewarding effects of MDMA, particularly those produced by R-(-)-MDMA.