Because of reported differences in potency, recombinant DNA-derived human alpha interferons (IFNs) were reevaluated for use against acute Herpes Simplex Virus type 1 (HSV-1) infection of the rabbit eye. The IFNs used topically were IFN-alpha2(IFN-α2) and a consensus of known human IFN-αs, designated IFN-αCon. Prophylactic treatment with IFN-αCon, at 1 or 15×106U/eye/day beginning 48 hours before HSV-1 inoculation and therapeutic treatment with 5 or 15×106U/eye/day beginning 4 hours after inoculation with either IFN-αCon1or IFN-α2appeared to prevent or significantly reduce the development of corneal epithelial involvement. The effects were dose dependent with no evidence for decreased activity at the higher dose. The duration of HSV-1 shedding into tear film was not significantly reduced.