We have studied the ability of a purified preparation of leucocyte interferon (IF) to augment human antibody-dependent cell-mediated cytotoxicity (ADCC). The IF preparation was added to cultures of the ADCC assay consisting of peripheral blood mononuclear target cells, a sensitizing human antiserum specific for the HLA antigens expressed on the target cells, and effector cells obtained from the peripheral blood of healthy human subjects. Increased cytolysis was found at each of four effector to target cell ratios but could be demonstrated only at concentrations of the sensitizing antiserum of 2.5% and lower. Removal of monocytes from the effector cell population did not decrease the level of cytotoxicity, and isolated monocytes were unreactive, suggesting that K cells (the subpopulation of lymphocytes mediating ADCC) were susceptible to augmentation. Since it is widely accepted that IF can augment spontaneous cytotoxicity mediated by natural killer (NK) cells, our results provide further evidence that human NK and K cells are the same or similar subpopulations or that the mechanisms regulating the activities of these cells are similar. Furthermore, our findings suggest that IF treatment can improve the discriminatory power of the ADCC assay in detecting transfusion or transplantation related immunity.