A goldfish NMDA receptor (NMDAR) cDNA was used to analyze NMDAR RNA expression during optic nerve regeneration. Following crush of the optic nerve, NMDAR RNA levels initially decrease and then increase in retinal ganglion cells. This latter increase corresponds with the time when ganglion cell axons are forming stable connections with their targets in the optic tectum. NMDAR RNA stability assays indicate that the increase in this RNA is largely a result of increased NMDAR gene expression. This increase requires return of electrical activity in the regenerating axons, interaction between ganglion cell axons and their targets in the optic tectum, and functional NMDARs in the postsynaptic tectal cells. These requirements for induction of presynaptic NMDAR RNA are similar to those proposed for synapse stabilization during development and regeneration of the visual system and during long-term potentiation (LTP) in the hippocampus.