Target antigens relevant for immune reactions in inflammatory liver diseases should be expressed on the hepatocellular membrane. Using mechanically or enzymatically isolated rabbit hepatocytes, we evaluated the influence of cell integrity on the detection of membrane-expressed antigens by sera from patients with chronic hepatitis and by murine monoclonal antibodies. Our results provide evidence that target antigens of liver membrane autoantibodies (LMA) as well as liver kidney microsomal antibodies (LKM) are not expressed on the hepatocellular membrane of viable and intact isolated rabbit hepatocytes. However, LMA were detected in the sera of 56% of patients with autoimmune chronic active hepatitis using mechanically isolated hepatocytes. These findings underline the diagnostic relevance of the autoantibodies. It is suggested that LMA are directed against constituents of the cytoskeleton. Therefore, it seems to be unlikely that this antibody is causally involved in the pathogenesis of autoimmune liver diseases.