The immunopathological role of T-lymphocytes in Herpes Simplex Virus type-1 (HSV-1) induced stromal keratitis (SK) has been well established, however, many questions still remain as to the actual mechanism(s) involved in the expression of this disease. To address this issue we have depleted mice of CD4+ and CD8+ T-lymphocytes at various stages of the disease and evaluated the effect of this therapy on the clinical outcome of the disease. We found that depleting mice of CD4+ T-lymphocytes either ameliorated the disease or halted its further progression. In contrast, depleting animals of CD8+ T-lymphocytes exacerbated or had no effect on the outcome of the disease. The results of this study suggest that CD4+ T-lymphocytes are involved in both the induction and the expression of SK, and CD8+ T-lymphocytes may serve some regulatory function in this disease.