The cell biology and biochemistry of the asialoglycoprotein receptor (ASGP-R) system provide unique insights into the fundamental process of receptor-mediated endocytosis. This chapter focuses on specific aspects of the structure, morphology, and functions of the ASGP-R during receptor-mediated endocytosis. It presents comparisons with other systems of receptor-mediated uptake of macromolecules. The ASGP-R is an integral membrane glycoprotein the isolation of which requires detergent. Under these conditions, the receptor retains a fraction of its original ligand-binding activity. In the presence of nonionic detergent, the ASGP-R from rabbit or rat liver is approximately 250,000 daltons as determined by gel filtration or sedimentation equilibrium analysis. The ASGP-R from each species is a glycoprotein composed of oligosaccharides in N-linkage, primarily to asparagine residues. In addition to oligosaccharide modification, the ASGP-R is posttranslationally modified by the addition of phosphate residues.