Abstract 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused transient alterations in vitamin E levels in every brain region examined. However, vitamin E returned to normal levels within a few hours in all brain regions but the substantia nigra, where at 2 days vitamin E levels first rose above normal levels. Vitamin E deficient mice were much more susceptible to MPTP toxicity than controls, in terms of lethality and DOPAC depletion in the substantia nigra. However, in the same vitamin E deficient mice, the striatum was partially protected from neurotransmitter and metabolite depletion by MPTP. The mechanism of toxicity of MPTP may differ in the striatum and the midbrain.