Studies were conducted to determine if treatment of mice with methamphetamine (METH) would produce a loss of dopaminergic cells in the substantia nigra. The number of TH+/Nissl-stained was significantly decreased in both Swiss-Webster (S-W) and C57bl mice (approx. cell loss of 40% and 45%, respectively) 5-8 days after treatment with METH. In these same mice there was a corresponding decrease in neostriatal dopamine (DA) content (90% and 92%, respectively). In parallel studies, treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produced similar neuropathological effects. The finding that nigral cell loss occurs after METH treatment indicates that the METH-treated mouse may be a very relevant model of Parkinson's disease (PD).