Spleen cells from uninfected CBA mice are more cytotoxic for Sendai virus-infected L929 cells than for uninfected cells and the lymphocytes responsible have the properties of NK cells. Preincubation of spleen cells with culture supernatants from Sendai virus-infected L929 cells increases the cytotoxicity for uninfected target cells. This increase in cytotoxicity can also be produced by pretreatment with purified mouse interferon. The enhancing effect of both the infected culture supernatants and purified interferon can be neutralized with anti-interferon serum. It is concluded that the preferential killing of Sendai virus-infected L929 cells by NK cells is dependent on the induction of interferon and that interferon will increase NK cell cytotoxicity for uninfected target cells.