This study investigated the immunohistochemical localization of nestin and its expression level in the brains of mice infected with scrapie, a disease which is characterized by spongiform neurodegeneration, neuronal vacuolation, and astrogliosis. Western blot analysis showed that the protein level of nestin was significantly increased in scrapie-infected brains compared with those of control brains. Nestin immunoreactivity in vascular endothelial cells was more intense in the brains of scrapie-infected mice compared with those of controls. There was marked nestin immunostaining in reactive astrocytes, but not in the neurons of the scrapie-infected brains. Considering all the findings, this study suggests that the nestin-positive cells, including glial cells and vascular endothelial cells, may have the potential to differentiate into mature glial cells and other neuronal elements, which would replenish lost neurons.