Mice carrying large established major histocompatibility complex (MHC) class 1+ sarcoma tumors can be successfully treated by immunization with genetically engineered sarcoma cells transfected with syngeneic MHC class II plus B7-1 genes. This approach is significantly more effective than previously described strategies using cytokine- or B7-transduced tumor cells which are only effective against smaller tumor loads, and which cannot mediate regression of longer-term established tumors. The most efficient tumor rejection occurs if both the class II and B7-1 molecules are coexpressed on the same tumor cell. Immunity induced by immunization with class II+B7-1(+)-transfected sarcoma cells involves CD4+ and CD8+ T cells, suggesting that the increased effectiveness of the transfectants is due to their ability to activate both of these T cell populations.