The effects of recombinant preparations of human interferon-gamma (rIFN-gamma) and tumor necrosis factor (rTNF), alone or in combination, on class I or class II major histocompatibility complex (MHC) antigen induction were studied using K562, a multipotent hematopoietic precursor cell line. Class I antigens were weakly induced by rIFN-gamma; however, rTNF at any concentration examined (1-1000 U/ml) showed no effect on the induction of class I or class II antigens in the cells. rIFN-gamma (600 U/ml) induced approximately 20% of the cells to express class I antigens after 72-h exposure, whereas 81% of the cells demonstrated class I antigens on their cell surfaces when the cells were simultaneously exposed to 600 U/ml of rIFN-gamma and 1000 U/ml of rTNF. The class II MHC antigens were not induced by the treatments with rIFN-gamma or rTNF, alone or in combination. A synergistic increase of mRNA for class I MHC molecules was demonstrated by treatments of the cells with rIFN-gamma and rTNF in combination. rTNF, but not rIFN-gamma, weakly induced granulocyte-monocyte antigens on the cell surface; however, no synergism was observed on the induction of these antigens by the combined treatments with rIFN-gamma and rTNF. These results indicate that class I MHC antigen expression on K562 cells can be induced by IFN-gamma in cooperation with TNF in a manner different from myeloid antigen expression.