Abstract: The topical administration of a plasmid encoding a Type I interferon such as interferon &agr;1 (IFN-&agr;1) to the cornea has potent anti-herpes activity. The expression of the interferon transgene in the corneas of infected individuals is transient and short-lived. The plasmid protected mice from HSV-1-induced encephalitis in a dose- and time-dependent manner when applied to the cornea prior to infection. The method may be used to treat or prevent herpes infections not only in the eye, but also in other portions of the oropharyngeal region, and in other mucous membranes including the genitalia. Patients presenting with acute or reactivated herpes infections are topically treated with DNA encoding a Type I interferon, where the DNA is not designed to integrate into the genome, but is placed under the control of a promoter that will cause expression of the interferon while the DNA persists in the cells that take it up.