Nestin is a neurofilament protein expressed by the immediate precursors to neurons and glia in rats and humans. Nestin immunoreactivity in the rat CNS was studied following kainic acid (KA) hippocampal lesions. Numerous nestin positive cells within the KA lesion were confirmed to be reactive astrocytes by their immunoreactivity for glial fibrillary acidic protein (GFAP). The number of these cells decreased with time after the KA lesion and no astrocyte immunostaining for nestin was observed in control animals. A subset of nestin-positive cells in the ventricular subependymal region appeared to be radial glial cells, extending to cell body layers. Nestin is one of several embryonic markers expressed by reactive astrocytes, suggesting an embryonic reversion induced by the KA lesion, possibly to enhance functional recovery.