The antiviral activity of idoxuridine (5-iodo-2'deoxyuridine, IDU), trifluorothymidine (F3TDR), and 5-methylamino-2'deoxyuridine (MADU) were compared on a double-blind basis by noting the effect of topical administration of the drugs on the severity of epithelial herpetic keratitis in rabbits. F3TDR was clearly more effective in eliminating herpetic lesions than either idoxuridine or MADU. The virus content of infected corneas was determined while under treatment with idoxuridine and F3TDR, after antiviral treatment, and throughout placebo treatment. The F3TDR was more effective in lowering the virus titer, and this lowering appeared to be correlated with the epithelial healing. Prolonged treatment prevented a rise in virus titer, which had been seen after shorter periods of idoxuridine therapy. There was no evidence of corneal toxicity after treatment with high concentration of F3TDR in man and animals.