The ability of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce parkinsonism has focused attention on potential endogenous or exogenous toxins that may follow similar uptake and conversion pathways to selectively target mitochondrial function in dopaminergic neurones. Exposure to such agents, together with a genetically determined susceptibility, is an attractive working hypothesis for the cause of Parkinson's disease. New insights into the mechanism of action of MPTP and its analogues are presented together with evidence supporting the potential role of endogenously produced toxins in the death of dopaminergic neurones in Parkinson's disease.