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 com- monly occurs in cirrhosis. This abnormality might result in impaired clearance of desialylated glycoproteins from plasma. (HEPATOLOGY 1992;15:702-706.) The asialoglycoprotein receptor (ASGP-R) is a transmembrane glycoprotein present on hepatocytes in all mammals studied, including humans (1-3). Although some controversy exists regarding the distribution of the ASGP-R on the surface of the rat hepatocyte, most investigators have found about 70% of the receptor on the sinusoidal surface, about 30% on the lateral membrane and none on the canalicular surface (4-8). The ASGP-R is thought to clear the plasma of asialoglycoproteins (i.e., glycoproteins that lack a sialic acid group on the terminal position of the glycoprotein side chain),