Human interferon gamma (HuIFN-gamma) was found to prevent herpes-simplex virus (HSV 1) induced keratitis in monkey eyes, when administered topically at concentrations of greater than or equal to 3 X 10(5) reference units/ml. Protective efficacy demonstrated with lower concentrations of HuIFN-gamma in combination with low titers of HuIFN-alpha provided evidence of synergistic interferon activity in vivo. Tolerance problems observed in eyes affected by virus inoculation seem to be attributable to the experimental conditions including species heterology.