The clinical and electroretinographic features of chronic methanol intoxication are scarce, and neurotransmitter studies have not been conducted. In addition, most of the studies in the field include results after acute administration. In the present work, a chronic methanol intoxication scheme (2 g/kg/day ip for 2 weeks) was carried out in Sprague-Dawley rats previously depleted of folates with methotrexate. Taurine (2%) in drinking water was also administered in two groups of animals. Blood formate levels were increased in methotrexate-methanol-treated animals with respect to controls (0.98 +/- 0.09 and 0.30 +/- 0.03 mM, respectively). Amino acids and monoamines were determined in plasma and in retina, optic nerve, hippocampus, and posterior cortex by HPLC with fluorescence or electrochemical detection. The main finding was an increased aspartate content in the optic nerve in methotrexate methanol-treated animals. Methanol alone increased glutamate, aspartate, glutamine, taurine, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid levels in the hippocampus and 5-hydroxytryptamine in the retina. Taurine administration had no significant effect on changes induced by methanol treatment. We concluded that chronic methanol administration produced accumulation of aspartate, an excitotoxic amino acid, in the optic nerve. These findings contribute to the understanding of methanol neurotoxicity and might indicate a relationship between chronic methanol consumption and the development of optic neuropathies.