To study the effect of immunosuppression on the development of murine cytomegalovirus (MCMV) retinitis, BALB/c mice were immunosuppressed with methylprednisolone (a corticosteroid) and/or with antibodies against CD4+ and CD8+ T cells and inoculated with low-dose MCMV (5 x 10(2) plaque-forming units) by the supraciliary route. Nonimmunosuppressed mice inoculated with low-dose MCMV by the supraciliary route did not develop necrotizing retinitis. By contrast, 78-100% of immunosuppressed mice developed retinitis after inoculation of low-dose MCMV. To study the effect of depletion of individual T cell subsets, mice were depleted of either CD4+ or CD8+ T cells and inoculated with low-dose MCMV by the supraciliary route. The frequency of retinitis in CD4-depleted mice (30%) was not significantly different from that of nonimmunosuppressed control mice (0%). The frequency of retinitis in the CD8-depleted group (80%) was similar to that observed in mice immunosuppressed with corticosteroid alone (90.9%), with antibodies to both T cell subsets (100%), or with steroid and both T cell subset antibodies (100%). These results support the conclusion that the CD8+ T cell subset is responsible for control of ocular MCMV infection. Furthermore, these results suggest that the CD8+ T cell subset may be important in preventing ocular CMV infection in immunosuppressed patients.