The extraordinary versatility of the antibody-forming mechanism in producing an almost limitless number of specific receptor sites complementary for almost any molecular conformation of matter within a size range (1-3) represented by a hexa-or heptasaccharide as an upper and a mono-or disaccharide as a lower limit, is almost certainly related to the unique structural features of immunoglobulins and differentiates them from all other known proteins. These antibody-combining sites are formed as a consequence of the interaction of two polypeptide chains, a light and a heavy chain (2, 4, 5). The antibodies usually formed to various antigens often represent heterogeneous populations of immunoglobulin molecules of different classes, subclasses, and genetic variants and also show specificities tgward different antigenic determinants (1, 2, 6, 7). In some instances, however, relatively homogeneous populations of antibodies with respect to many of these properties have been obtained. Among these have been human antibodies to dextran and levan (8, 9) and rabbit antibodies to the group-specific carbohydrate of streptococcus (10-12), antibodies to the Type III-specific capsular polysaccharide of pneumococcus (13,14), rabbit antihapten (15), and specimens of antibodies and of Fab' fragments which crystallized (Nisonoff et al., in references 16,17), but sequence data on these are not yet available.The large body of sequence data related to immunoglobulin structure comes from the analysis of urinary Bence Jones proteins and from the monoclonal immunoglobulins found in large amounts in the sera of patients with multiple myeloma and Waldenstrtim macroglobuUnemia (16,18). While a substantial body of evidence was available relating these proteins to immunoglobulins, the recent demonstration that many myeloma globulins have specific ligand-binding properties like those of many antibodies provides increasing confidence that myeloma globulins represent homogeneous populations of antibody molecules (16,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).

Sequences of the third complementarity determining region of antibody heavy chains (CDRH3s) are listed according to their length. Human sequences vary from 2 to 26 amino acids residues, but less extensively in other species. When combined with the other five complementarity determining regions, this enormous length variation of CDRH3, together with amino acid substitutions in their sequences, can provide a very large number of antibody specificities and can influence the shape of antibody combining sites.