Peripheral blood lymphocytes (PBLs) of normal subjects and of kidney allograft recipients treated with immunosuppressive drugs (azathioprine and prednisone) were tested for natural killer (NK) cell activity against K562 cells, and for killer (K) cell activity against L-1210 cells in the presence of rabbit anti-L-1210 antiserum. It was found that the natural cell-mediated cytotoxicity (NCMC) was abolished in the immunosuppressed patients while the antibody-dependent cell-mediated cytotoxicity (ADCC) remained normal. Furthermore, no correlation was observed between both activities in the treated group, whereas a strong positive correlation did exist in the control population. Uremic routinely hemodialyzed patients tested for NK cell activity did not exhibit any significant difference with the control group. These data indicate that NCMC and ADCC are different functions, apparently correlated in normal population but discriminated by immunosuppressive medical treatment. The abrogation of NCMC in patients in whom the risk of malignancy is highly increased strengthens the concept of a crucial role of NK cells in the in vivo surveillance toward malignancies.