Effects of various fractions of methanol extracts from fruiting bodies of Cordyceps sinensis on the lymphoproliferative response, natural killer (NK) cell activity, and phytohemagglutinin (PHA) stimulated interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) production on human mononuclear cells (HMNC) were studied. Two of the 15 column fractions (CS-36-39 and CS-48-51) significantly inhibited the blastogenesis response (IC50 = 71.0 +/- 3.0 and 21.7 +/- 2.0 micrograms/ml, respectively), NK cell activity (IC50 = 25.0 +/- 2.5 and 12.9 +/- 5.8 micrograms/ml, respectively) and IL-2 production of HMNC stimulated by PHA (IC50 = 9.6 +/- 2.3 and 5.5 +/- 1.6 micrograms/ml, respectively). TNF-alpha production in HMNC cultures was also blocked by CS-36-39 and CS-48-51 (IC50 = 2.7 +/- 1.0 and 12.5 +/- 3.8 micrograms/ml, respectively). These results indicated that neither CS-36-39 nor CS-48-51 was cytotoxic on HMNC, and that immunosuppressive ingredients are contained in Cordyceps sinensis.