Uniocular injection of herpes-simplex virus type 1 into the anterior chamber of BALB/c mice induced contralateral retinitis with relative preservation of the ipsilateral retina. Overall 95% of T-cell deficient nude mice developed ipsi- and contralateral retinitis, suggesting the importance of T-cells in this model. We then depleted lymphocyte subsets in susceptible BALB/c and resistant CB-17 and C57BL/6J mice using anti-CD4 (helper/inducer cells) or anti-CD8 (suppressor/cytotoxic cells) monoclonal antibody. 85% of CD8-depleted, 58% of CD4-depleted and 50% of untreated BALB/c mice developed contralateral retinitis. All CD4- and CD8-depleted animals developed severe ipsilateral retinitis. These results suggest that CD8 cells (but not CD4 cells) are protective for the contralateral retina in BALB/c mice and that both subsets are important for the ipsilateral protection. In CB-17 and C57BL/6J mice, depletion produced no change in the contralateral retina but resulted in ipsilateral retinitis, suggesting different mechanisms for ipsi- and contralateral protection. The possible role of the anterior-chamber-associated immune deviation is discussed.