Murine splenocytes immunized in vitro against syngeneic adult kidney fibroblasts coupled sequentially with a glycylglycylcystamide spacer, and the p-nitrophenyl ester of muramyl dipeptide developed direct cell-mediated cytotoxicity to the immunizing cells which cross-reacted against syngeneic fibrosarcoma cells. These results extended previous observations showing the reverse pattern of cross-reactivity. Derivatized kidney fibroblasts also gave protection in an in vivo protection-challenge experiment performed with the tumor cells. A hypothesis is presented relating this kind of autoimmunity to tumor immunity.