Cytomegalovirus (CMV) retinitis is an important ocular complication in human immunodeficiency virusinfected individuals and the leading cause of blindness in those not undergoing highly active antiretroviral therapy. Murine CMV (MCMV) infection of mice has been shown to be a useful small-animal model for the study of CMV pathogenesis in the eye. The purpose of this study was to evaluate CMV persistence in ocular tissue and to determine the potential for reactivation. Following subretinal inoculation of immunocompetent BALB/c mice, tissues were tested for infectious virus by plaque assay and for the presence of viral DNA and RNA by PCR. The latent phase of the infection in mouse tissues was analyzed by plaque assay, PCR, and explantation cocultivation in both immunocompetent and cyclophosphamide-treated mice. The acute phase of the infection was resolved by 2 to 3 weeks postinfection, while viral DNA persisted beyond 12 months. Immediate-early 1 transcripts were detected in 100% of the ocular samples tested, and glycoprotein H transcripts were detected in 86% of the samples, but no difference in viral DNA or RNA levels between immunocompetent and immunosuppressed animals was measured. Irrespective of immune status, no in vivo reactivation was detected; however, reactivated virus was observed in 76 to 82% of the eyes following explantation onto a permissive cell layer. The transcriptional activity and relatively high frequency of explantationinduced reactivation in both immunocompetent and immunosuppressed mice suggest that control of MCMV latency in ocular tissue might involve other regulatory events that are not entirely dependent on intact specific immunity.Cytomegalovirus (CMV) is a -herpesvirus that is fairly ubiquitous in the human population and generally causes mild or subclinical disease in healthy individuals (47). Although the acute replication of CMV is eventually cleared by the host immune system, the virus persists by establishing a lifelong latent infection, defined as the presence of viral DNA without the detection of infectious virus. Human CMV (HCMV) has been shown to establish latency in cells of the monocyte/macrophage lineage including hematopoietic progenitor cells (16,42,56), and there is evidence of persistent HCMV infection in aortic endothelial cells (14,15). The ability of CMV to reactivate from a latent state that is subsequently accompanied by asymptomatic viral shedding can periodically occur in healthy, seropositive individuals; however, the specific cell types from which recurrent virus comes are unknown. A significant amount of CMV morbidity can be attributed to reactivation events that are normally controlled by the immune system, based on the observation that immunosuppressed individuals often suffer from HCMV disease (54).CMV has emerged as an important opportunistic pathogen in immunosuppressed persons, and reactivation of latent virus, which can cause significant morbidity in multiple organs including the eye, is frequently observed (20,48). CMV retinitis is a focal, progress...