Many inherited polymorphisms in plasma proteins and in enzyme activities of red blood cells are now available as genetic markers to differentiate bloods within a species (see Giblett, 1969, and Harris, 1975). However, the term “blood groups” is still usually retained to describe antigenic differences detected on the red cell surface by means of specific antibodies. Macromolecules occurring in secretions of the same or different species which carry serological specificities related to the red cell antigens are called blood group substances; these substances are designated by the letter or symbol assigned to the corresponding antigen on the red cell surface. In man fifteen well-defined independent blood group systems are recognized, each comprising antigens believed to be the products of alleles at one gene locus or of closely linked gene loci. In addition, there are some very frequent (“public”) and infrequent (“private”) antigens which may belong to established systems or may be parts of new systems (see Race and Sanger, 1975). For only three blood group systems, namely ABO, Lewis, and P, is the chemical nature of the antigens unequivocally established, and this review will be primarily concerned with these systems.