The ability of rostral raphe neurons to transport tritiated proline to other areas of the brain was measured in neurons taken from rats 3 weeks after the administration of 20 mg/kg MDMA, given SC twice daily on 4 consecutive days, 10 mg/kg fenfluramine IP, 4 injections given every 2 h, or saline. The effects of MDMA on proline transport were compared with the effects of 5,7-DHT administration (along with pargyline and desipramine, to reduce damage to NE neurons). A different set of rats were also killed 3 weeks after fenfluramine, MDMA, 5,7-DHT or saline to compare 5-HT and 5-HIAA levels in brain. Anterograde (forward) transport of tritiated proline was measured in slices via scintillation counter, and autoradiograms were taken to visualize injection site. Levels of 5-HT and 5-HIAA were measured in homogenates via HPLC. Correlations between pooled (within treatment) data for amount of transported material, 5-HT and 5-HIAA were performed. Degree of tritiated proline transport and levels of 5-HT and 5-HIAA were similar in fenfluramine-treated, MDMA-treated and 5,7-DHT treated rats. All animals demonstrated decreased regional transport of proline, and reduced levels o 5-HT and its metabolite. However, reduced proline transport appeared less severe than reduction in 5-HT and 5-HIAA, especially in the hypothalamus, thalamus and striatum. This study is important because most measures of MDMA-induced serotonergic neurotoxicity assess functioning of the serotonin system, which makes it difficult to distinguish between down regulation of serotonergic functioning and actual damage to axons. Some have suggested the apparent swelling and fragmentation of serotonergic axons after high dose MDMA is a misleading measure of neurotoxicity, because that the axons survive but have less serotonergic activity. The current study used a non-serotonergic measure of axonal functioning and found that MDMA, fenfluramine, and a classical serotonergic neurotoxin (5,7-DHT) all produced long term decreases in axonal transport. This suggests that serotonergic axons are either absent or not working properly and that they have not selectively down regulated serotonergic activity. This finding is consistent with earlier research investigating axonal transport after neurotoxic regimens of parachloroamphetamine.