AZT inhibited replication of an immunodeficiency-inducing strain of feline leukemia virus (FeLV-FAIDS) in vitro at concentrations as low as 0.005 microgram/mL. This antiviral activity was augmented an additional 25-30% when AZT was combined with human recombinant alpha-interferon (2b) (IFN alpha). Administration of AZT alone or in combination with IFN alpha, beginning at the time of exposure to a 100% persistent viremia-inducing dose of FeLV-FAIDS, abrogated the progression of viral infection and protected treated animals from induction of persistent antigenemia and disease. Low levels of antigenemia were detected intermittently in some AZT-treated cats throughout the 6 week treatment and 40 week observation period. Combination of AZT with IFN alpha appeared even more effective than AZT alone. In this treatment group even transient antigenemia was undetectable throughout the therapy and posttherapy observation periods, and latent virus could not be reactivated from bone marrow cells of protected animals. These results provide additional evidence that early treatment with AZT or AZT/IFN alpha therapy can be effective in completely aborting retroviral infections.