Glycophorin A, the major human erythrocyte sialoglycoprotein, is found exclusively on cells of the erythroid lineage. The amino acid sequence is known, and glycophorin A isolated from mature erythrocytes contains a single N-glycosidic and 15 O-glycosidic oligosaecharides. Monoclonal antibodies against erythrocyte glycophorin A reacted weakly with erythroid precursors while a monospecific rabbit antiserum reacted strongly with immature and mature red cells.Glycophorin A was isolated from cells representing various stAges of erythropoiesis in normal bone miarirow, from blood cells of neonates with erythroblastosis fetalis, and from the erythroleukemic cell lines K562 and HEL before and after induced differentiation. Analysis of the oligosaccharides showed less O-glycosylation of glycophorin A in erythroid precursors.The degree of glycosylation increased concomitantly with differentiation.The major sialoglycoprotein of human erythrocytes, glycophorin A (GPA), consists of 131 amino acids distributed in three separate domains: at the cell surface, within the lipid bilayer, and in the cytoplasm (1). The external NH2-terminal portion is highly glycosylated, containing one N-glycosidic oligosaccharide at Asn-26 and 15 O-glycosidic oligosaccharides. The structure of the N-glycosidic oligosaccharide has been determined (2). Most O-glycosidic oligosaccharides have the structure Neu5Aca2-3Gall31-3(Neu5Aca2-6)GalNAc (ref. It was shown that GPA is confined to the erythroid cell lineage and appears at the basophilic normoblast stage of erythropoiesis (5, 6). GPA is also found on the erythroleukemia cell lines K562 (7) and HEL (8,9). The biosynthesis of the protein has been extensively studied in K562 cells and its N-and O-glycosylations have been elucidated (10-12).We have now isolated GPA from normal bone marrow precursor cells and from the K562 and HEL cell lines before and after induction of differentiation, and we have studied its oligosaccharides. Our