Excitotoxic oligodendroglial death is one of the mechanisms which has been proposed to underlie demyelinating diseases of the CNS. We describe here functional consequences of excitotoxic lesions to the rabbit optic nerve by studying the visual evoked potentials (VEPs) measured in the visual cortex. Nerves were slowly infused with the excitotoxin kainate a subcutaneously implanted osmotic pump which delivered the toxin through a cannula onto the optic nerve. Records of VEPs were obtained before pump implantation and at 1, 3 and 7 days post-implantation, and weekly evaluated thereafter for up to 4 months. We observed that the VEPs generated by light stimuli progressively changed in both amplitude and profile after the lesion as well as in comparison to those generated in control animals infused with vehicle. Histological examination of the damage caused by the excitotoxic insult showed that large areas of the optic nerve were demyelinated and their axons distorted. These observations were confirmed and extended by immunohistochemical analyses using markers to neurofilaments, myelin basic protein and the oligodendrocyte marker APC. The results of the present paper indicate that the consequences of excitotoxicity in the optic nerve share functional and morphological alterations which are found in demyelinating disorders. In addition, this experimental paradigm may be useful to evaluate the functional recovery of demyelinated optic nerves following various repair strategies.