Persistent mydriasis seen in cats used in an oncology study apparently was not related to neoplasia. Ophthalmoscopically, the cats had severely atrophic retinas and clinically observable visual impairment. These findings were confirmed by electroretinographic and histologic examination. Cats with these retinal lesions had received combinations of methylnitrosourea, ketamine hydrochloride, and feline leukemia virus. Retinopathy was not seen in ketamine-anesthetized cats receiving feline leukemia virus. To test the nature of this phenomenon, four cats were given both drugs and three received methylnitrosourea alone. The four cats developed severe generalized retinal degeneration by day 5, whereas the three cats given methylnitrosourea alone had normal retinas. Histologic changes in the affected cats were extensive loss of rods and cones, and of the outer nuclear layer. The electroretinographic responses to white light were depressed or extinguished. Retinal degeneration, therefore, appeared to be dependent upon administration of both methylnitrosourea and ketamine hydrochloride.