A cDNA library from the human hepatoma cell line Hep G2 was prepared in the expression vector lambda gt11. Using specific antibodies, a cDNA clone containing the entire coding sequence for the human asialoglycoprotein receptor was isolated and sequenced. The deduced amino acid sequence of 291 residues is very homologous to the sequence of the major asialoglycoprotein receptor protein from rat. The comparison shows that there is no significant post-translational processing and no leader sequence, cleaved or uncleaved, at the amino terminus. An internal signal sequence, probably the membrane-spanning segment, residues 41-59, is assumed to direct insertion of the carboxyl-terminal ligand binding portion of the receptor across the endoplasmic reticulum membrane.