Human red blood cell membranes contain four sialic acid-rich glycoproteins, denoted as glycophorins (GPs), that carry the antigens of the MNSs and Gerbich (Ge) blood group systems. The MNSs locus corresponds to two related and adjacent genes that encode the polypeptide sequences of two of these molecules: GP A and GP B. The structural differences between the major polymorphic antigens M and N or S and s are determined by amino acid heterogeneities within the glycosylated NH2-terminal domain of GP A or GP B, respectively. Because the NH2-terminal 26 residues of GP B are identical with those of GP A possessing blood group N specificity, the former molecule carries an additional N antigen, denoted as 'N'. Apart from the major antigens, GP A and GP B carry several high- or low-frequency receptors that are encoded by the MNSs locus. Additional alleles are apparently silent or produce GP A-GP B hybrid molecules. The Ge locus is similar to the MNSs locus in that it appears to correspond to the adjacent genes encoding the polypeptide chains of GP C and GP D. However, the Ge system does not include antigens that are polymorphic in Caucasoids. Because all GPs are heavily glycosylated, oligosaccharides, in addition to protein, are involved in antigens of the MNSs and Ge systems. The carbohydrate units on all GPs account for additional antigens that are not part of the MNSs or Ge systems.