Following inoculation of HSV-1 (KOS strain) into the anterior chamber of one eye of a BALB/c mouse, the virus travels to the uninoculated contralateral eye and contributes to the devastating retinal necrosis which occurs in this eye 10-12 days p. i. In parallel experiments, HSV-2 (MS strain) was inoculated uniocularly via the anterior chamber route; animals were sacrificed at intervals and their eyes removed for histopathology and virus culture. Histopathological examination revealed that, in contrast to the retinal destruction observed in HSV-1 inoculated animals, the retina of the contralateral eye of HSV-2 injected animals was unaffected. Culture studies demonstrated that, similar to the spread of HSV-1 after anterior chamber inoculation, HSV-2 reached the contralateral eye in two temporally separate waves and also revealed that the amount of virus recovered from the uninoculated eye of HSV-2 infected animals was significantly less than that recovered from the uninoculated contralateral eye of HSV-1 injected mice. Further examination demonstrated that animals inoculated with HSV-2 via the anterior chamber route did not develop the suppression of virus-specific delayed hypersensitivity (DH) which is characteristic of HSV-1 induced anterior chamber associated immune deviation (ACAID). Taken together, the sparing of the contralateral retina and the ability to generate a virus-specific DH response suggest that DH assists in the preservation of the contralateral retina of animals inoculated with HSV-2 via the anterior chamber route by limiting virus replication and the amount of virus which reaches the uninoculated eye.