The molecular basis for the structural diversity of antibody combining sites has become apparent through the recent X-ray diffraction studies on several immunoglobulin (Ig) fragments (see Davies et al. 1975a,b for a review). These structures reveal that the combining site is formed by bringing together the three hypervariable regions (Wu and Kabat 1970) of VL and of VH to form a continuous complementarity-providing surface. A quantitative comparison of the tertiary structures of a number of variable domains from both light and heavy chains has demonstrated that their nonhypervari-able or framework regions are very similar, with the principal differences occurring in the hypervariable loops (Padlan and Davies 1975).\ud \ud In view of this structural in variance, the immunoglobulin variable region can be regarded as consisting of a rigid framework to which are attached the hypervariable loops. These loops are not large, generally consisting of at most 17 residues; in addition, the configurations..