Ocular signs are common features in approximately 70% of patients with acquired immune deficiency syndrome (AIDS). The most frequent signs are retinal cotton wool spots, retinal hemorrhages, retinal edema, and areas of necrosis. These retinal pathologies are produced by the many opportunistic ocular infections, including cytomegalovirus (CM), Cryptococcosis, Toxoplasmosis, Candida, Mycobacterium, herpes simplex herpes simplex virus, varicella zoster virus, histoplasmosis, and syphilis which have been reported in the retina of AIDS CM rarely causes retinitis in healthy adults. The first case of CM chorioretinitis in a normal adult was reported in 1959. This was followed by only 2 more case reports in the next decade. By 1980, approximately 40 adult patients with CM retinitis had been described primarily in immunosuppressed organ transplant recipients. At present, it is estimated that 22,500 AIDS patients have had CM retinitis. Untreated CM retinitis inevitably leads to irreversible retinal necrosis and blindness in AIDS patients. Because human CM is species-specific, it has not been possible to use this virus in an animal model system. We have recently confirmed that the guinea pig CM provides an excellent model for the investigation of cogenital CM infections of the inner ear, and have been able to demonstrate the prophylactic effects of ganciclovir in this model as well as to perform pharmokinetic studies. However, the guinea pig lacks a vascular retinal, and is therefore an unacceptable model for CM retinitis. Recently an ocular model using mouse CM has been described following IP inoculation. This model demonstrated infectious virus in the eye but no ocular pathology. We now propose to ascertain the optimal experimental conditions for a murine CM retinitis model using immunosuppression with cyclosporine A plus antilymphocyte serum, monoclonal antibodies to CD-4 + lymphocytes, macrophage, B lymphocytes, or combinations of these agents to mimic the effects of HIV immunodeficiency in human CM retinitis. The following basic questions concerning the pathogenesis of immunosuppressed murine CM infections will be investigated: 1) what are the characteristics of murine CMV infection within the ocular system of immunocompetent and immunosuppressed mice? 4) can this model be used to determine the role of the immune system in CMV retinopathy? 5) does this model system provide a bioassay to test the efficacy of ganciclovir treatment? An interdisciplinary approach is used to investigate the clinical symptoms, immunologic, virologic, electrophsiologic, morphologic, and pathologic aspects of the model of immunosuppression induced murine CMV retinitis.