Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mammals causes damage to the nigrostriatal pathway similar to that observed in Parkinson's disease. In the present study, we have investigated alterations in cell death effector gene expression induced by the neurotoxin MPTP in mouse substantia nigra. Intraperitoneal MPTP injections in mice resulted in a significant increase in bax mRNA by about two- and three-fold after 3 and 6 days, respectively. The up-regulation of bax mRNA was associated with concomitant increase in Bax immunoreactivity observed mainly in large- and medium-sized neurons in the substantia nigra that are destined to die. Our results indicate a pathophysiological significance of bax, which promotes programmed cell death, in MPTP neurotoxicity.