The effects of 1 to 100 MuM MDMA, 4-methylthioamphetamine (4-MTA) and 4-methylthiomethamphetamine (4-MTMA) on serotonin (5-HT) transport and release and 5-HT-mediated aortic contractions were investigated in rat brain, synaptosomes and aortic tissue. 5-HT release and transport was assessed via measuring levels of tritiated 5-HT. MDMA, 4-MTA and 4-MTMA, at 100 mcM, all blocked transport of 5-HT, and 5-HT transport was partially blocked by all substances at 50 mcM. While all three substances induced 5-HT release from synaptosomes, MDMA induced greater 5-HT release than 4-MTA or 4-MTMA at identical doses. Contractions were measured in isolated descending thoracic aortae by examining changes in isometric tension after exposure to each of the substances. Both 4-MTA and 4-MTMA significantly reduced 5-HT mediated contraction in aortic tissue. MDMA, on the other hand, failed to induce significant reductions in aortic contraction. None of the substances elicited aortic contractions without the presence of 5-HT. Findings in synaptosomes confirm what is already known about the pharmacology of MDMA. Research findings also suggest that MDMA does not interact with non-neuronal 5-HT transporters, since it did not alter 5-HT mediated aortic contractions in vitro. The authors hypothesize that differences ability to reduce 5-HT mediated aortic contractions are associated with 5HT2A receptor activity, with 4-MTA and 4-MTMA reportedly 5HT2A antagonists and MDMA a 5HT2A agonist.