We have investigated the mechanism by which flavone-8-acetic acid (FAA) acts to enhance immune responsiveness in murine tumor model systems. Analysis of spleen mRNA samples after FAA administration indicates that both interferon (IFN) Alpha and tumor necrosis factor (TNF) mRNA can be detected within 1-3 hours. We have now found flavone can act directly on mouse macrophage cell lines in vitro and induced specific cytokine gene expression. These results indicate that FAA acts by directly stimulating gene expression of immunoregulatory proteins.