AIM: To evaluate the role of local interleukin 6 (IL-6) in the pathogenesis of acute and chronic liver disease. METHODS: The cellular site of IL-6 in cryostat sections of liver from 31 patients with liver disease was examined using indirect immunofluorescence with a monoclonal antibody. RESULTS: IL-6 staining in sinusoidal endothelial cells was very noticeable and diffusely distributed in the lobules of specimens of acute viral hepatitis. IL-6 expression in endothelial cells, particularly in necrotic areas of hepatocytes, was increased and was accompanied by enhanced expression in Kupffer cells. In contrast, IL-6 staining in infiltrating mononuclear cells was prominent in portal tracts, and the numbers of cytokine positive cells were greater in specimens of chronic active hepatitis compared with chronic persistent hepatitis. In non-specific reactive hepatitis intrahepatic expression of IL-6 was minimal, while in alcoholic liver fibrosis the cytokine distribution in the lobules was similar to that of acute viral hepatitis. CONCLUSIONS: These results indicate that locally produced IL-6 contributes to the inflammatory process and immunological response in acute and chronic liver disease.