The requirements for fully effective antiviral chemotherapy of herpes simplex eye disease are described, and the status of currently available therapy is outlined. The principles of in vivo assessment of antivirals by measuring the corneal infectivity titre using the multiple microinoculation technique are described. This technique has been used to determine optimal schedules of topical administration of interferon for prophylaxis or therapy of viral eye disease. This led to the design of a clinical trial that has proved the beneficial effect of exogenous interferon in preventing recurrences or recrudescences of ulcerative herpetic keratitis. The method of measuring corneal infectivity titres has limitations, however, when very potent antivirals are used. These limitations have been overcome by the development of a Corneal Epithelial Lesion Reduction Assay (CELRA). It resembles a plaque reduction assay, and provides a means of measuring antiviral effect over a wide range of activity. The significance is discussed of results with adenine arabinoside, adenine arabmoside 5′ monophosphate, and a deaminase inhibitor.