Neurotoxic effects of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) were evaluated in vitro using a human neuronal cell line, SH-SY5Y, that contained features contributing to expression of MPTP toxicity in vivo, namely, a transport system for dopamine (DA) and monamine oxidase (MAO) activity. In this model system,MPTPwas found toreducelevels of catecholamines (DA,norepinephrine, epinephrine), serotonin (5-HT), and the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA). MPTP enhanced 3H-DA release, which could contribute to the reduction in DA concentrations seen in these cells. In addition, MPTP inhibited MAO activity (Ki 2.26 10 5 M). Pretreatment with the MAO inhibitor pargyline protected the cells from MPTP-induced alterations of catecholamines and the decrease in 5-HT. In this in vitro model, the cholinergic antagonists atropine and d -tubocurarine also protected cells from MPTP-induced alterations of catecholamines. The capability of cholinergic antagonists to prevent the MPTPinduced alterations of catecholamineconcentrations suggests a possiblecholinergic contribution to MPTP neurotoxicity in this cell line.