We investigated the effect of immunosuppressive substance (ISS) on the immune responses mediated by interleukin 2 (IL 2). The induction of LAK cells was intensely inhibited by a high concentration of ISS (1000 micrograms/ml), but a low concentration of ISS (250-500 micrograms/ml) had no affect on the generation of LAK cells. ISS had no ability either to neutralize the activity of IL 2, or to compete with IL 2. Endogenous production of IL 2 in PHA response was not reduced by ISS, but the expression of the IL 2 receptor in the PHA response was significantly suppressed by ISS. These results suggest that ISS exerts its inhibitory effect on immune response-mediated IL 2 through modification of the IL 2 receptor.