Interleukin-10 (IL-10), a novel inhibitory cytokine, is one of Th-2 (T helper) cytokine. It inhibits mixed lymphocyte reaction, and the production of inflammatory cytokine and monokine downregulates major histocompatibility complex antigen (MHC) class II antigen expression. However, the effect of IL-10 on tumor cells is not known. Therefore, the mechanism of tumor tolerance induced by IL-10 was investigated. (WKA rat fetus-derived fibroblast) (WFB) and W14 and W31 (EJ-ras oncogene transformants of WFB) were cultured with recombinant human (rh)IL-10 (0, 10, 50, 100 ng/ml). FACS analysis was performed using the following monoclonal antibodies: anti-rat MHC class I monoclonal antibody; and monoclonal antibody 109 (anti-natural killer [NK] target molecule on W14). Monoclonal antibody (mAb) 109-defined antigens were newly expressed during the transforming process by EJ-ras oncogene transfection to WFB. In addition, the effects of rhIL-10 on the ability of proliferation and susceptibility to NK cells were assessed. The cultivation with rhIL-10 resulted in a dose-dependent decrease in the expressions of MHC class I antigen and monoclonal antibody 109-defined antigen. The proliferation and susceptibility to NK cells of W14 were inhibited. These data demonstrated a possibility that IL-10 could induce tumor tolerance to host immunity by inhibiting the expression of tumor-associated antigens and MHC class I.