The pro-toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is widely used to create animal models of Parkinson's disease. This unit describes protocols for the production of stable and substantial lesions in the dopaminergic nigrostriatal pathway of mice and non-human primates. The models can be employed for assessing the neural mechanisms underlying the development of Parkinson's disease and for screening potential therapies for the treatment of this condition.