Poly I:C, an interferon inducer, was found to have a definite therapeutic effect in experimental herpes simplex keratitis. In the two strains tested, however, this effect was minimal. It was far less than many other drugs, including IDU. Topical or systemic treatment of acute lesions with Poly I:C did not decrease the death rate from encephalitis, and did not significantly reduce the rate of recurrences of keratitis. The continued topical use of the drug provided some protection to the cornea for six to eight weeks but, after that time, the cornea actually seemed more susceptible to recurrences of disease even though administration of Poly I:C was continued. Herpes simplex virus is a poor inducer of interferon, and is relatively resistant to interferon action. Even a potent interferon inducer, such as this double-stranded RNA, seems relatively ineffective in the treatment of herpetic keratitis, or in the prevention of recurrences. © 1969.