Tumor cell variants were derived from the BW5147 T-cell lymphoma that differ in major histocompatibility complex (MHC) class I antigen expression, tumorigenicity and metastatic potential. In general, increased H-2Kk expression was found to be correlated with a reduced tumorigenicity and spontaneous metastasis. CD8+ T cells were identified in the immune recognition of such variants, implicating a role for H-2Kk in the presentation of tumor-associated antigens. In the present study, H-2Kk+ BW variants were transfected with a gene encoding interferon-gamma (IFN-gamma), a potent inducer of MHC class I expression. The resulting transfectants exhibited an increased expression of H-2Kk and concomitantly an inability to generate visible tumors and a reduced metastatic capacity. Furthermore, immunization with the IFN-gamma transfectants resulted in an increased generation of cytotoxic T lymphocytes (CTLs) that lysed both the transfectants and the parental tumor cells. Based on these results, vaccinations with the IFN-gamma transfectants were performed against the parental tumor cells. The results clearly demonstrated that such vaccinations reduced significantly the tumorigenicity and metastatic capacity of the parental tumor cells. Hence, in this tumor model, IFN-gamma gene transfection provides a means to immunogenize H-2Kk+ BW tumor cells.