A light microscopic study was done to investigate retinal changes in healthy and immunosuppressed mice after intraocular inoculation of murine cytomegalovirus (MCMV). A 0.01-ml inoculum containing 10(5) plaque-forming units of MCMV was placed behind the lens in 138 4-week-old Swiss Webster mice. Ninety-eight mice were immunosuppressed with 0.2 mg/g of cyclophosphamide given intraperitoneally at the time of inoculation and 0.1 mg/g of cyclophosphamide every 5 days thereafter. Selected eyes were examined on postinoculation days 5, 10, 15, and 16-20. Evidence of viral infection was most prominent in uveal tissue. Uveal infection developed whether or not animals received cyclophosphamide, but retinal necrosis developed only in immunosuppressed mice. Focal retinal necrosis, primarily involving the outer retinal layers and retinal pigment epithelium, was first observed in an eye examined on day 10. Retinopathy from MCMV was present in three of five eyes (60%) examined on day 15, and in six of 16 eyes (37.5%) examined between days 16-20. Retinal disease was characterized by full-thickness retinal necrosis, scattered cytomegalic cells, intranuclear and intracytoplasmic viral inclusions, and acute and chronic inflammation. These results indicate that MCMV can produce a necrotizing retinopathy in mice and that immunosuppression facilitates infection. Although ocular MCMV infection in immunosuppressed adult mice is a potential model for study of human CMV retinopathy, many differences exist between human CMV and MCMV and between the ocular diseases they produce.