The severity of HSV stromal keratitis varies among inbred mouse strains, with A/J and BALB/c>C57BL/6. Since cell-mediated immunity (CMI) is thought to play a role in the pathogenesis of HSV stromal keratitis, we measured the proliferative response of primed splenic mononuclear cells (SMC) from these strains to HSV antigen in vitro.Primed SMC from all three strains showed increased thymidine uptake after incubation with UV-inactivated HSV-1 antigen (UV-HSV) in vitro when compared with control antigen. Uptake by SMC from BALB/c and A/J mice was greater than that by SMC from C57BL/6 mice. The difference between BALB/c and A/J was not significant. Uptake by non-primed SMC cultured with UV-HSV was not significantly greater than uptake induced by control antigen.Thus, among the strains studied, A/J and BALB/c mice, which are relativelysusceptibleto stromal keratitis, have thegreatestproliferative response to UV-HSV antigen. C57BL/6 mice, which are relativelyresistantto stromal keratitis, have theleastresponse. These findings suggest that genetically determined differences in CMI may influence the course of HSV keratitis and are consistent with the hypothesis that the host immune response plays a role in the pathogenesis of HSV stromal keratitis.