Serum concentrations of asialoglycoproteins are increased in cirrhosis. We hypothesized that this increase results from abnormalities in the asialoglycoprotein receptor, which is located on the sinusoidal and lateral membrane of hepatocytes. Therefore we searched for morphological alterations in the distribution of the asialoglycoprotein receptor in human liver, using a light microscopic immunoperoxidase method in autopsy livers. In 24 of 25 (96%) of patients without liver disease, the asialoglycoprotein receptor was located on the sinusoidal and, less prominently, the lateral surface of hepatocytes but not the canalicular surface. In contrast, in 12 of 18 (67%) patients with cirrhosis of various causes, the receptor also was localized strikingly along the canalicular surface, with a corresponding decrease on the sinusoidal and lateral surfaces. We conclude that an abnormal cell-surface distribution of the asialoglycoprotein receptor commonly occurs in cirrhosis. This abnormality might result in impaired clearance of desialylated glycoproteins from plasma.