The relative efficacy of 5-methoxymethyldeoxyuridine (MMUdR), adenine arabinoside (Ara-A), 5-iododeoxyuridine (IUdR) and the combination of MMUdR and Ara-A in the treatment of experimental herpes simplex keratitis was investigated in rabbits. Treatment was initiated either at 4 or 24 h post virus inoculation. The parameter used to evaluate effectiveness was lesion size. Each eye was graded daily for the first 5 days and on alternate days thereafter to day 11. At concentrations of 2 or 5% both MMUdR and Ara-A were found to have potent antikeratitis activity. At 5% concentration, Ara-A provided essentially the same protection against herpes keratitis as 0.1% IUdR, while MMUdR was slightly less effective. The simultaneous application of 2% MMUdR and 2% Ara-A in combination was more effective than 5% MMUdR alone and was as effective as 5% Ara-A or 0.1% IUdR in controlling the viral keratitis.