Radix Tripterygium wilfordii Hook-F (TW) is a Chinese herbal medicine that has been reported to be effective in the treatment of various autoimmune disorders in experimental animals and man. Little is known about the immunosuppressive mechanism of action of this medicine. We demonstrate herein that TW is capable of inhibiting several afferent immune functions including the in vitro response of human peripheral blood mononuclear cells to both mitogen and alloantigen, and the generation of cytotoxic T cells. This inhibition is likely mediated through a reduction in both IL-2 production and IL-2 responsiveness. TW evidenced little capability of impairing IL-2 receptor expression, or efferent immune mechanisms such as cell-mediated cytotoxicity or natural killer cell-mediated cytotoxicity. The immunosuppressive effects of TW were reversible except at the highest concentration tested, 2.4 micrograms/ml, and there was no evidence of TW-mediated cell-well damage as evidenced by trypan-blue exclusion. TW, or some of its constituents, may be important new agents to be studied for immunosuppression in organ transplantation.