We have studied the effect of cortisone acetate (CA) on two important biological functions: (1) on NK cell-mediated cytotoxicity of B6D2F1 mice to T cell lymphoma, YAC-1 and (2) on hybrid resistance of mice to parental B6 bone marrow grafts. Results of our experiments have shown that 5 mg of CA administered i.p. was effective in significantly decreasing NK cell cytotoxic potential. The effect of CA was prompt, since a significant decrease in NK cell cytotoxicity was observed already 3 h after CA administration. This effect was, however, rather short-lasting since the NK cell cytotoxicity of CA-treated mice was comparable to that of control mice 120 h after treatment. As to the mechanism of NK cell decrease, it appears that CA affected NK cell cytotoxicity directly, since the attempts to identify suppressor cells in CA-treated mice failed. Because NK cells and bone marrow effector (BME) cells were shown to bear close resemblance, we have investigated also whether a decrease in NK cell cytotoxicity would be reflected by a decline in BME cells rejection potential. Indeed, when resistant B6D2F1 hybrid mice were pretreated with 5 mg of CA, 48 h before transplantation of 10(6) B6 parental bone marrow cells, the growth of B6 marrow cells was detected 7 or 8 days later in the spleens of B6D2F1 hybrid mice. These experiments indicated that bone marrow rejection potential was also weakened by CA treatment, and moreover, demonstrated further correlation between BME cells and NK cells.