A costimulatory signal from B7–1 (CD80) to its counter-receptor CD28 is required for T-cell activation. Many tumors, including most human leukemias, lack expression of B7–1, and this has been suggested to contribute to the failure of immune recognition of these diseases. A murine leukemia model system was developed to assess the potential role of B7–1 in the induction immunity to leukemia cells. The nonleukemic 32Dc13 myeloid cell line was transformed by transfection of the BCR/ABL gene, generating a subline (32Dp210/clone 26) that was leukemic and rapidly lethal to syngeneic, immunocompetent C3H/HeJ mice or T-cell-deficient nude mice. B7–1-modified leukemic cells remained lethal in nude mice, but caused only a transient, nonlethal leukemia in C3H/HeJ mice. After a single exposure to live, nonirradiated B7–1-modified leukemic cells, C3H/HeJ mice developed protective immunity against subsequent challenge with B7–1(-) leukemic cells. Further, hyperimmunization with B7–1(+) leukemic cells prolonged the survival of mice previously injected with a lethal number of B7–1(-) leukemic cells. These results indicate that myeloid leukemic cells may be attractive candidates for B7–1 gene transfer.