The effects of 20 mg/kg IP MDMA administered twice daily across 4 days on central 5-HT uptake into synaptosomes and on 5-HT induced isometric contractions of aortic rings, with studies conducted in rats, and in tissue taken from MDMA-treated rats compared with saline-treated controls. Descending thoracic aortic rings were used in this study. Tritiated 5-HT was used to measure uptake and transport in synaptosomes and in aortic rings. Tissue removed and tested 1, 7, 14 and 21 days after MDMA treatment. Pre-treatment with MDMA reduced maximum rate of 5-HT uptake across all points in time in synaptosomes, and direct application of MDMA to tissues abolished 5-HT uptake. Maximum contraction of aortic rings was reduced after MDMA treatment on 1 and 7 days post treatment, but not on 14 or 21 days post-treatment. Neither MDMA pre-treatment or direct application of MDMA had any effect on 5-HT uptake into aorta 1 day post-treatment. These findings suggest that vascular tissue could be affected by chronic treatment with MDMA, but that MDMA (either as pretreatment or when directly applied) did not interfere with or alter 5-HT uptake into aortic rings. Central, rather than peripheral, mechanisms are proposed as producing this change. The authors hypothesize that MDMA could compromise vascular function in regular ecstasy users.