We have initiated the molecular definition of the antigens recognized by Gross MuLV-specific cytolytic T lymphocytes on the surface of Gross MuLV-induced tumor cells. A panel of target cells was obtained by the double transfection and expression of a retrovirus gene and a foreign H-2 gene in recipient mouse fibroblasts. Our results show that class I H-2 transplantation antigens have a directive influence in determining the antigenicity of proteins encoded by the gag and env MuLV genes. Genes not linked to H-2 influence the intensity and the specificity of the cytolytic T lymphocyte response to Gross MuLV-induced tumors. Finally, MuLV-induced antigens expressed by transfected fibroblasts induce tumor immunity and lead to accelerated tumor rejection in vivo.