Human neural stem cells have exhibited a remarkable versatility to respond to environmental signals. Their characterization in models of neurotoxic injury may provide insight into human disease treatment paradigms. This study investigates the survival and migration of transplanted human stem cells and tyrosine hydroxylase immunoreactivity in the parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model, using antisera recognizing human nuclear protein (hNuc) and tyrosine hydroxylase (TH). Our results indicate long-term (up to 90 days) survival of human stem cell xenograft in the MPTP-lesioned mouse and the presence of hNuc-immunoreactive cells at sites distal to the transplant core. Few TH-positive cells are identified in the striatum by immunoperoxidase staining and using immunofluorescent double labeling, infrequent TH-immunoreactive, transplanted cells are identified.