Inoculation of herpes simplex virus Type 1 into the anterior chamber of BALB/c mice induces a characteristic ocular infection involving primarily the anterior segment of virus-injected eyes and the retina of contralateral uninjected eyes. In the BALB/c strain, which is susceptible to herpetic retinitis, anti-HSV delayed hypersensitivity responses are actively suppressed, although anti-HSV antibody responses remain intact. We previously demonstrated that C57B1/6 mice, as well as (BALB/c×C57B1/6) F1are highly resistant to HSV-1 retinitis. Studies have now been performed to determine the relationship between systemic immune responses to HSV and the resistance of C57B1/6 and the (BALB/c×05761/6)F1to develop retinitis after inoculation of HSV into one anterior chamber. Despite the resistance to herpetic retinitis by B6 and F1mice, both strains developed a pattern of systemic immune responses to HSV similar to those observed in the susceptible BALB/c mice. Therefore, resistance to retinal infection with HSV-1 does not appear to correlate with the pattern of systemic cell-mediated or humoral immune responses to intracameral HSV-1.