In a detailed study of ocular infection by herpes simplex virus (HSV) type 1 in mice, the course and signs of eye disease were investigated and compared in primary and secondary infection using slit-lamp examination, culture of the tear film, and monitoring of the blink reflex. Response to primary inoculation ranged from subclinical infection to severe keratitis. Compared with conjunctival scarification, corneal scarification resulted in more frequent and severe eye disease and signs of CNS infection. Previous infection in the skin of the contralateral ear considerably modified subsequent infection of the eye so that signs of disease occurred earlier, were limited to dendritic keratitis with some stromal involvement, and were largely reversible. The mouse seems to be a suitable animal for studying ocular infection with HSV.