Human K562 leukemic cells were exposed in vitro to cis-diamminedichloroplatinum (DDP) followed by addition of intact or irradiated mononuclear cells (MNC) obtained from peripheral blood of normal donors. tumor inhibition provoked by DDP was significantly enhanced by normal MNC, but not by irradiated cells at the effector: leukemic cell ratio of 2:1. In contrast MNC alone did not show appreciable effects on K562 cells. The NK activity of MNC was also inhibited by exposure to gamma rays. The combined effects of DDP + MNC do not appear to be due to increased susceptibility of DDP-pretreated K562 cells to NK-mediated cytolysis. Actually leukemic cells treated with 10 micrograms/ml of DDP and cultured for 48 h at 37 degrees C, showed decline of susceptibility to the cytotoxic effects of MNC. These studies suggest that natural immunity could be of potential value in the clinical use of DDP.