Varied manifestations of herpes simplex keratitis are postulated to be related to alterations or paucity of protective immune response to the virus. In this study lymphocyte subpopulations and macrophage inhibition factor (MIF) assay are investigated in herpes simplex keratitis. Active T-lymphocytes are detected to be significantly low in active keratitis as compared to the healed stage (P less than 0.001) and normal control subjects (P less than 0.01). Active T-cells are also lower in bilateral keratitis than in unilateral keratitis (P less than 0.01), and in stromal keratitis than in epithelial keratitis (P less than 0.05). Total E-rosette-forming cells and leucocyte migration inhibition factor (MIF) assay demonstrates significantly lower values in bilateral keratitis than in unilateral keratitis, and in stromal keratitis than in epithelial keratitis. On healing, total E-RFC, active T-cells and MIF values improved and are comparable to those found in normal subjects. Enumeration of absolute lymphocyte counts and EAC rosette-forming cells (B-lymphocyte cells) did not yield any differences. Our observations demonstrate paucity of cell-mediated immune response in stromal keratitis. More marked deficiency is demonstrable in bilateral keratitis. Manifestations of herpes simplex keratitis and their healing is observed to be relatable to the level of cell mediated immune response.