It took approximately one century to discover the neuropathologic lesion responsible for Parkinson's disease, of which clinical manifestations were originally described in 1817. Namely, the lesion is located in the substantia nigra pars compacta and is histologically characterized by loss of pigmented nerve cells, formation of Lewy bodies and proliferation of astrocytes. The neuronal loss is observed predominantly in the lateral portion of the pars compacta, more conspicuously in its ventral region where immunoreactivity to tyrosine hydroxylase is also decreased. The formation of Lewy bodies, which are found to be peculiar in Parkinson's disease, may hold a clue to the elucidation of the mechanism of neuronal degeneration. An animal model induced by MPTP stimulates a search for environmental factors capable of initiating the disease.