Structural and functional alterations of α-synuclein is a presumed culprit in the demise of dopaminergic neurons in Parkinson's disease (PD). α-Synuclein mutations are found in familial but not in sporadic PD, raising the hypothesis that effects similar to those of familial PD-linked α-synuclein mutations may be achieved by oxidative post-translational modifications. Here, we show that wild-type α-synuclein is a selective target for nitration following peroxynitrite exposure of stably transfected HEK293 cells. Nitration of α-synuclein also occurs in the mouse striatum and ventral midbrain following administration of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Conversely, β-synuclein and synaptophysin were not nitrated in MPTP-intoxicated mice. Our data demonstrate that α-synuclein is a target for tyrosine nitration, which, by disrupting its biophysical properties, may be relevant to the putative role of α-synuclein in the neurodegeneration associated with MPTP toxicity and with PD.