The current study was designed to observe the effects of drugs used for the treatment of inflammatory diseases (glucocorticoid, aspirin, and gamma globulin) on interleukin 6 (IL-6) production in the liver which may be involved in acute phase protein stimulation. The HUH-7 hepatoma cell line was used in which the IL-6 gene is expressed and produces IL-6 in vitro. The cells were cultured in RPMI 1640 supplemented with 1% fetal calf serum for 12 h prior to addition of these drugs. We collected the cells and supernatants at 24 h, 48 h, and 72 h after addition of glucocorticoid, aspirin, and gamma globulin. IL-6 mRNA in the cells was measured by Northern blot hybridization, while the IL-6 activity in culture supernatants was measured by enzyme-linked immunosorbent assay. At 48 h after addition of glucocorticoid and aspirin, there was a suppression of IL-6 activity in the culture supernatants, which was associated with a decrease of mRNA level in the cells. However, suppression by gamma globulin was not observed. These data demonstrate that glucocorticoid and aspirin are potent regulators of IL-6 synthesis in the hepatoma cell. These components may decrease acute phase protein production via the suppression of IL-6 production in the liver during inflammation.