Studies have shown that interferons, or agents which induce interferon, are capable of antitumor actions. The two means by which interferons are believed to affect antitumor activities in vivo are: (1) a direct action on tumor cells resulting in inhibition of cell growth (anticellular activity), and (2) through indirect actions which result in the enhancement of tumoricidal activities of host cells. We intend to systematically analyze the anticellular activities of the three classes (Alpha,Beta,Gamma) of purified human interferons first, in vitro, then on the growth of these same human tumors in athymic nude mice. Due to the characteristic property of species specificity exhibited by human interferons, the antitumor effects in the nude mice bearing xenografts could only be due to a direct action of the human interferons on the human tumors. Conversely, antitumor activities caused by the inoculation of these animals with the three classes (Alpha,Beta,Gamma) of murine interferons would be due to the indirect actions on murine effector cells capable of expressing antitumor effects. The results of these studies will establish the possible mechanisms through which interferons inhibit tumor growth in vivo; the relative antiviral and anticellular activities of the different human interferons on the various human tumor cells; and whether the passive administration of the three types of murine interferons can activate the cellular elements (macrophages and NK cells) to destroy progressive human tumors in T-cell-deficient mice.