Retinal degeneration induced by a single parenteral dose (40 mg) of N-methyl-N-nitrosourea (MNU) was studied in rats and rabbits. Sequential observations showed that severe pathological changes, that is, complete or widespread destruction of the photoreceptor layer and the outer nuclear layer of the retina, occurred in both animals by 72 hr after the administration of MNU. At week 5, at the end stage of the retinal degeneration induced by MNU, thin remnants remained with the inner nuclear layer in direct contact with the pigment epithelium. An additional immunohistochemistry study using antibodies against 7-methyldeoxyguanosine (7-mdGua), revealed the presence of high levels of 7-mdGua DNA adducts in the nuclei of the outer nuclear layer cells. This finding suggests that the alkylation of the outer nuclear layer by MNU was the direct cause of the retinal degeneration seen in these animals.