Treatment with murine gamma-interferon (IFN) preparations of variant sublines of Friend leukemia cells resistant to the alpha, beta IFN-induced antiviral state (Affabris, E., Jemma, C., and Rossi, G.B. (1982) Virology 120, 441-452; Affabris, E., Romeo, G., Belardelli, F., Jemma, C., Mechti, N., Gresser, I., and Rossi, G. B. (1983) Virology 125, 508-512) results in the establishment of a bona fide antiviral state. In fact, gamma IFN preparations are able to induce a dose-dependent reduction of endogenous virus release and of vesicular stomatitis or encephalomyocarditis viruses yields (up to 1.5 log). Under these experimental conditions, no inducible 2-5A synthetase activity is detectable in cell extracts. The 67-kDa protein kinase, uninducible by treatment with alpha, beta IFN (up to 13,000 units/ml), is instead induced upon treatment with gamma IFN at a similar rate of activity as in wild-type Friend leukemia cells, both when assayed in solution and after immobilization on poly(rI) X poly(rC)-agarose.