Humans and nonhuman primates are uniquely sensitive to the toxic effects of methanol. The toxic syndrome in these species is characterized by formic acidemia, metabolic acidosis and blindness or serious visual impairment. Nonprimate species are normally resistant to the accumulation of formate and associated metabolic and visual toxicity. We have developed a nonprimate model of methanol toxicity using rats in which formate oxidation has been selectively inhibited. Methanol intoxicated rats developed formic acidemia, metabolic acidosis and visual toxicity analogous to the human methanol poisoning syndrome. Visual dysfunction was manifested as reductions in the flash evoked cortical potential and electroretinogram which occurred coincident with blood formate accumulation. Histopathologic studies revealed mitochondrial disruption and vacuolation in the retinal pigment epithelium, photoreceptor inner segments and opticnerve. The establishment of this nonprimate animal model of methanol intoxication will facilitate research into the mechanistic aspects of methanol toxicity as well as the development and testing of treatments for human methanol poisoning. (Supported by The American Petroleum Institute and NIH grants RO1-ES06648 and P30-EYO1931).