By means of indirect immunofluorescence microscopy, a peripheral fluorescence reaction with hepatocytes was found, surrounding the entire cell, with sera from patients with cancer and acute hepatitis and from normal blood donors. I t was proved that this reaction was not related to bile canaEculi, contrary to bile canaliculi antibody demonstrated previously from patients with cronic active liver disease. By using fluorescein-conjugated anti-human IgG, the reaction with the periphery of the hepatocytes was produced to a more or less pronounced degree with almost all sera studied. The reaction seems not to be directed against contractile proteins on the liver cell membrane as only a minor part of these sera had also IgG smooth-muscle antibody, and anti actamyosin antibody obtained by affinity chromatografy did not react with the hepatocyte. When applying fluorescein-conjugated anti-human IgM the reaction with the periphery o f the hepatocytes was observed in one fourth of the patients with acute hepatitis and only sera which contained also IgM smooth-muscle antibody.