Plasma lysozyme levels are elevated in several different pathological conditions. In our study we show that well differentiated human hepatoma cells Hep3B and HepG2 are active synthesis sites of lysozyme and that this synthesis can be modulated by acute phase mediators. The production and modulation of lysozyme synthesis was studied by means of Northern-blot analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a specific bioassay after treatment of the cells with interleukin-16, interleukin-6 and tumor necrosis factor-a. Hep3B and HepG2 cells constitutively synthesize high amounts of lysozyme. Lysozyme synthesis and secretion were found to be augmented by interleukin-16 and tumor necrosis factor-a in both cell lines. Interleukin-6 caused an increase in lysozyme production in Hep3B but a decrease in the HepG2 cells. As expected, the synthesis of albumin was decreased in both cell lines. Furthermore we demonstrated that HepG2 and Hep3B cells produce a biologically active form of the enzyme as measured by a specific bioassay. The results demonstrate that lysozyme is constitutively synthesized by Hep3B and HepG2 hepatoma cell lines and that lysozyme synthesis is modulated by acute-phase mediators. Well differentiated human hepatoma cells may respond differently todifferent cytokines. (HEPATOLOGY 1994;19:1182-1188.) Lysozyme is a ubiquitous enzyme catalyzing the hydrolysis of the p-(1,4)-glycosidic bond of bacterial peptidoglucan, a major component of the bacterial cell wall. The enzyme is secreted by cells of the exocrine glandula and by cells related to the immune system like macrophages and granulocytes (1-3). It is present in easily detectable amounts in human milk, tears, saliva and serum (1). Furthermore, the presence of lysozyme was previously demonstrated in various human (2) and rat tissues (4). Lysozyme may enhance the actions of immunoglobulins and phagocytic activity of macro-