The hybrid glycophorin in Dantu-positive human erythrocytes of the N. E. variety was not cleaved by treatment of intact cells with various proteases, in contrast to normal glycophorins. Therefore, it could be purified by phenol/saline extraction of membranes from trypsin-treated and chymotrypsin-treated red cells and subsequent gel filtration in the presence of Ammonyx-LO. The complete structure of the hybrid molecule, comprising 99 amino acid residues, was elucidated by sequence analyses of peptides prepared by chymotrypsin, trypsin, cyanogen bromide or V8 proteinase treatment. The N-terminal39 residues and the glycosylation of the molecule were found to be indistinguishable from those of blood-group-s-specific glycophorin B. Conversely, the residues 39 -99 were shown to be identical with the residues 71 ~ 131 of the major blood-group M-active or N-active sialoglycoprotein (glycophorin A). Hemagglutination inhibition assays revealed that the Dantu antigen represents a labile structure. The receptor might be located within the residues approximately 28-40 of the hybrid glycophorin, as judged from the effects of modifications of membranes. Our data provide an explanation for the previous findings that Dantu-positive cells (N. E. type) exhibit a protease-resistant N antigen and a qualitatively altered s antigen.The antigens of the MNSs blood-group system are located on two NeuAc-rich homologous glycoproteins in human erythrocyte membranes that are denoted as GP A (MN SGP or a) and GP B (Ss SGP or 6). The ' M N S s blood-group locus' appears to correspond to the adjacent genes that encode the polypeptide sequences of these two molecules (for reviews see Indirect evidence suggests that some alleles (Mi-V , J.R., English En) at the MNSs Iocus produce hybrid molecules of [3 -51).