Abstract The possible neurotoxic effects of the α-ethyl homologue of MDMA, N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), were examined following a regimen of twice daily dosing for four days. The levels of norepinephrine, serotonin and its metabolite 5-HIAA were quantitated by standard HPLC-EC techniques. In addition, the number of 5-HT uptake sites was estimated by examining the binding of [ 3H]-paroxetine to rat cortex homogenate. With 20 mg/kg (IP) subacute dosing of MDMA, a nearly 60% reduction in 5-HT, 5-HIAA, and 5-HT uptake sites was found, with no change in NE, two weeks posttreatment. A behaviorally equipotent dose of MBDB (25 mg/kg, IP) also produced a significant decrease in the serotonergic markers, 5-HT, 5-HIAA and [ 3H]-paroxetine binding sites. However, a comparison of the relative toxic effects of MDMA and MBDB indicates that MBDB may be slightly less neurotoxic. It was also found that MDMA but not MBDB caused a significant increase in dopamine levels at 3 hours following a single IP injection. The results are discussed in relation to the therapeutic index of MBDB and the relative importance of dopamine release in the neurotoxicity of MDMA.