OBJECTIVE: To study the apoptotic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the nigral dopaminergic neurons of mice and 1-methyl-4-phenylpyridium ion (MPP+) on pheochromocytoma (PC12) cells, as well as the antagonism of Eldepryl against MPTP's apoptotic effect. METHODS: Three groups of C57BL mice were treated with MPTP, Eldepryl plus MPTP and normal saline, respectively, for 7 days before performing TUNEL (terminal deoxyneucleotidyl transferase-mediated dUTP-x nick end labeling) and FACS (fluorescence activated cell sorting) analyses of neuronal apoptosis in the substantia nigra. The same tests were employed in cell culture to examine apoptosis in PC12 cells treated with MPP+, MPTP or PBS. RESULTS: Intraperitoneal administration of MPTP 30 mg/kg could induce nigral apoptosis, and oral use of Eldepryl prior to MPTP treatment could completely prevent the nigral apoptosis caused by MPTP. MPP+, an intermediate metabolite of MPTP, could lead to the apoptosis of PC12 cells, whereas MPTP itself had no such effect on PC12 cells. CONCLUSIONS: The experiment indicated that the neurotoxin, MPTP, might cause the death of nigral neurons through a mechanism of apoptosis and this effect might be mediated by its bioactive intermediate metabolite MPP+. Eldepryl could protect the neurotoxicity from MPTP.