In this study, we tested whether expressing an allogeneic MHC class I gene and/or a cytokine gene in tumor cells could induce anti-tumor immunity. We compared the potential therapeutic benefit of introducing IL-12 or H-2Kb alone and in combination into CT26 tumor cells. Whereas IL-12 expression in CT26 cells delayed the formation of tumors, the expression of class I molecules alone was apparently insufficient to reduce tumorigenicity. The combined expression of IL-12 and H-2Kb, however, more efficiently reduced tumor growth than did either genes alone. Histological examination of tumors expressing IL-12 and H-2Kb showed a non-specific inflammatory reaction, such as a necrosis, and an increased tissue infiltrate of immune effectors. These results suggest that the combined expression of IL-12 and H-2Kb in tumor cells has potential therapeutic benefit.