The effect of daily injections of 3 x 10(6) units of human leukocyte IF on the spontaneous cytotoxicity of peripheral lymphocytes was studied in 43 patients with a variety of diseases. An increase in spontaneous cytotoxicity was observed 12 to 24 h after the first IF injection with the peak of activity occurring, in most cases, at 24 h. In some patients a decrease in spontaneous cytotoxicity, observed 6 h after the injection, preceded this increase. The increment in spontaneous cytotoxicity was not significantly correlated to preinjection level of cytotoxicity, disease, age, sex, previous therapy, leukocyte counts or proportions of lymphocytes and monocytes. A second injection of IF maintained the spontaneous cytotoxicity at an increased level and during prolonged IF therapy, up to 9 months, the cytotoxicity remained elevated. IF treatment in vitro caused an enhancement of spontaneous cytotoxicity in lymphocytes drawn prior to IF injection. This IF-induced increase in cytotoxicity in vitro was correlated to the increase in cytotoxicity induced by IF in vivo. Six hours after the first IF injection the ability of IF in vitro to enhance spontaneous cytotoxicity was decreased and during prolonged therapy the ability of IF in vitro to enhance spontaneous cytotoxicity remained decreased.