Natural killer (NK) activity in rats and NK and antibody-dependent cell-mediated cytotoxicity in mice have been shown to be rapidly augmented by in vivo treatment with a variety of viruses and immune adjuvants. Poly I:C and other interferon inducers also caused boosting in NK-cell activity, with peak levels occurring at about the time of peak interferon levels. Crude and purified virus-induced interferon itself had strong boosting effects in mice, both when inoculated in vivo and when incubated briefly with normal spleen cells. The in vitro activation by interferon or by poly I:C was completely abrogated by anti-interferon. Interferon also appears to play a central role in augmentation of human NK-cell activity. Inoculation of normal volunteers with influenza virus or of a patient with poly I:C produced rapid boosting. In vitro incubation of peripheral blood mononuclear cells with various interferon preparations for 1 hour or overnight usually produced an appreciable increase in lytic activity.