N-Methyl-D-aspartate receptor subunit 1-like immunoreactivity (NMDAR1-LI) was investigated in the brain of Rana pipiens during optic nerve regeneration. Following unilateral optic-nerve crush, frogs were tested for prey-catching and optokinetic nystagmus responses to assess return of visual function. At 1, 2, 3 and 5 months after the surgery, NMDAR1-LI was assessed in central visual pathways. At 3 and 5 months, conspicuous ipsilateral NMDAR1-LI fibers were detected in the thalamic and pretectal nuclei, and the time of their appearance coincided with the onset of behavioral recovery. Also, only ipsilateral retinorecipient layers in the optic tectum showed increased NMDAR1-LI during optic nerve regeneration. These results suggest that NMDA receptors may be present on retinal ganglion cell axons and terminals that have been misrouted during regeneration.