AbstractSubunits of immunoglobulins have been prepared by two methods, both of which have contributed to our knowledge of the structural basis of antibody specificity. The first method is enzymic hydrolysis with either papain or pepsin and leads to the unequivocal conclusion that each combining site is contained in a fragment (Fab) of about 45,000 molecular weight and formed from the light chain and the N‐terminal half of the heavy chain, the Fd fragment. The second method of preparing subunits is to reduce the interchain disulfide bonds and to isolate the chains. This should decide whether the combining site is in the Fd fragment, the light chain, or is formed jointly by both. In fact, considerable loss of affinity for the antigen follows, whatever technique is used to dissociate the peptide chains and, although many papers have been published on this subject, no definite answer has yet been obtained. Although the majority opinion probably favors the view that both chains are concerned in the formation of the combining site, our tentative conclusion is that the site is placed entirely in the heavy chain and that the light chain has only a semispecific role in facilitating the reformation of the native configuration of the heavy chain after its disruption under the conditions necessary for dissociation of the two chain