The expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in the livers of 11 patients with chronic hepatitis B was studied immunohistochemically by light and electron microscopy to clarify the role of these adhesion molecules in tissue damage in chronic hepatitis B. On hepatocytes, ICAM-1 expression was confined to the bile canalicular surface when the liver inflammation was mild. In contrast, when the liver inflammation was severe, ICAM-1 was distributed on the entire surface of the hepatocyte, including the sinusoidal and lateral membranes; lymphocytes which were mostly positive for LFA-1, were often observed invading deeply among these hepatocytes. The degree of ICAM-1 expression on the hepatocytes was also related to the expression of HLA class 1 antigen. In liver showing diffuse expression of ICAM-1 on the hepatocytes, strong expression of HLA class 1 antigen was observed, and amounts of HBV in the liver were decreased. Diffuse expression of ICAM-1 and HLA class 1 antigen was mostly observed after acute exacerbation of liver inflammation. These results suggest that the ICAM-1/LFA-1 pathway is involved in the immunological mechanism responsible for liver cell damage in chronic hepatitis B.