Highly purified preparations of two recombinant-DNA derived human leukocyte interferon subtypes (LeIF-A and LeIF-D) and a similarly derived fibroblast interferon were compared for efficacy against herpes simplex virus, type 1, infection of the rabbit cornea. LeIF-D appeared to be more effective than LeIF-A especially when compared on the basis of interferon units. The fibroblast interferon showed no significant effects. The greater activity of LeIF-D compared with LeIF-A could be due to greater direct antiviral effects, as observed in rabbit cell cultures.