The antiviral effect of recombinant mouse interferon-beta (rMuIFN-beta) on herpes simplex virus type 1 (HSV-1) in experimentally infected mice was examined at several stages of infection as a model for the treatment of human HSV infection. Recombinant MuIFN-beta protected mice from lethal intraperitoneal challenge with virulent HSV-1 strains. The in vitro reactivation of HSV from latently infected trigeminal ganglia was also suppressed by treatment with rMuIFN-beta. Thus, rMuIFN-beta was effective against HSV-1 during acute infection and during in vitro reactivation of latent HSV. However, rMuIFN-beta was not effective in preventing the establishment of latent infection, or in eliminating a previously established latent infection.