Direct comparison of the effector cells mediating natural killer (NK) activity against mouse tumor cells and antibody-dependent cell-mediated cytotoxicity (ADCC) against mouse tumor target cells coated with alloantisera Indicated that NK cells and K-cells (effector cells mediating ADCC) may belong to the same subpopulatlon of lymphocytes, but they have a different mechanism of killing. Effector cells mediating NK activity and ADCC were nonadherent, nonphagocytic Fc receptor-bearing cells that sediment at 3.5–4.5 mm/hour. Treatment with anti-Thy 1.2 serum in the absence of complement resulted In an Increase of NK activity, whereas this treatment caused a substantial loss in ADCC. Both NK activity and ADCC were equally sensitive to the In vivo or in vitro effects of X-irradiatlon. In vivo inoculations of high doses of hydrocortisone resulted in a reduction of NK activity, but ADCC was not affected. NK cells were trypsln-sensitlve, with a profound decrease in the cytolytic activity being observed in a 4-hour⁵¹Cr release assay. The activity, however, could be recovered after overnight incubation at 37° C. Trypsin treatment did not Inhibit ADCC as measured by the 18-hour assay.