In an effort to establish the appropriate timing of myeloschisis repair, changes in the exposed neural tissue were studied during fetal development. Neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) were examined immunohistochemically in mice with vitamin-A-induced myeloschisis. As in the normally developing lumbosacral spinal cord, NSE was already expressed in the cytoplasm of neurons in the basal plate of the neural plaque in 16-day-old embryos. GFAP became positive at day 17 both in normal embryos and at the outer border of the plaques in dysraphic embryos. Expression of both NSE and GFAP in normal controls was unchanged in intensity and localization during later fetal development. In contrast, the expression of GFAP increased during later development in the neural plaque of dysraphic animals and suggests a progressive gliosis of tissue with the passage of time. The expression of NSE in the plaque did not change during this time. These results suggest that the neural plaque retains intact neurons in the face of progressive gliosis. Moreover, the results suggest that repair of the myeloschisis should start before irreversible changes are established by progressive gliosis.