The mechanism of action of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) is being studied in several animal species. In primates, NMPTP produces a persistent parkinsonian syndrome. Neurochemical studies have demonstrated a close correspondance between idiopathic Parkinson's disease in humans and NMPTP toxicity. Depletion of dopamine from the putamen and caudate nucleus is most pronounced, dropping to 3.5% of pre-NMPTP treatment levels. However, in the rat, guinea pig, and cat, equivalent chronic neurotoxicity cannot be produced. Acute pharmacological effects of high doses of NMPTP have been observed in these species, but even chronic NMPTP treatment diminishes dopamine content by only 40-60% in the nigro-striatal system of the guinea pig. Radiolabelled NMPTP has been prepared to determine the pattern its metabolism in several animal species. Autoradiographic as well as tissue punch techniques have demonstrated the selective localization of NMPTP in the caudate nucleus and putamen of the monkey brain, but its non-selective distribution in rat and guinea pig brain. The high pressure liquid chromatographic pattern of brain metabolites formed from labelled NMPTP is species specific. The determination of the toxic metabolic path in the monkey is being studied to learn how a peripherally administered, relatively small organic molecule can produce a specific neurochemical lesion, and whether this mechanism is relevant to idiopathic Parkinson's disease.