The U937 cell, a human monoblast cell line, has been used as a model to study the function of human monocytes. We investigated the effects of interferon-gamma (IFN-gamma) on superoxide anion (O2-) production, cell surface antigens, and cytokine production of U937 cells. IFN-gamma treatment enhanced O2- production of fMLP or PMA-stimulated U937 cells. IFN-gamma increased the ratio of CD23 and CD11b positive cells. The fluorescence intensity of CD14 and CD25 was enhanced by IFN-gamma treatment. U937 cells produced IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha by lipopolysaccharide (LPS) stimulation. IFN-gamma treatment enhanced TNF-alpha production, but decreased IL-6 production. These results suggest that IFN-gamma differentiates U937 cells to monocyte-like cells and it regulates the production systems of IL-6 and TNF-alpha separately in U937 cells.