Acute administration of the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the C57B1/6 mouse caused a rapid decrease in the amount of striatal tyrosine hydroxylase (TH), a marker of dopaminergic neurons, followed by a large increase in the astrocyte protein, glial fibrillary acidic protein (GFAP). The astrocyte (GFAP) response declined to baseline 3 weeks after administration of MPTP. Administration of a second dosage of MPTP at this time evoked a second GFAP response. The magnitude of the second response, however, was decreased in comparison to the response seen after only a single exposure to MPTP. Increasing the initial dosage of MPTP resulted in greater reductions of the second GFAP response. These data indicate that damage to striatal dopaminergic neurons reduces the signal available for initiating a second astrocyte response to MPTP.