The serum myeloma proteins are characteristic products of malignant plasma cells, and individual myeloma proteins provide an important source of information on the protein-producing capacities (and limitations) of plasma cell clones. The globulins produced by malignant plasma cells are closely related to the normal v-globulins, but immunochemical studies of the antigenic determinants present on myeloma proteins have uniformly shown that myeloma proteins are antigenically deficient when compared to normal y-globulins (1)(2)(3)(4)(5)(6)(7)(8). Similar studies (9-13) have shown that macroglobulinemic macroglobulins are antigenically deficient when compared to the normal 71-macroglobulins. Antigen deletion has been demonstrated to occur with malignant transformation (14), and antigenic deficiency of myeloma proteins could be viewed as reflecting a plasma cell change associated with malignancy. Alternatively, myeloma protein differences may simply reflect differences between normal y-globulin molecules (and between normal plasma cells). Immunochemical studies have not settled this question, although marked variability in the antigenic determinants on individual myeloma proteins has been noted. A number of studies, however, have emphasized systematic differences among the proteins formed in malignant plasma cells. Such proteins are now identified as Bence Jones proteins, y-myeloma proteins, fl2A-myeloma proteins, or yi-macroglobulins on the basis of specific immunochemical and physicochemical properties (15-18). Systematic differences of another type, however, may also occur within these four major groups.. Two antigenically different groups of Bence Jones proteins have been identified in several laboratories (19)(20)(21)(22)(23). Two types of y-myeloma proteins were identified by Korngold and Lipari (7), and Franklin (24) found two types of 82A-myeloma proteins. The molecular differences within major y-globulin groups has received less attention than the y-, 82A-, yLm-, and BJgrouping, and the presence of two general subdivisions has not been established as a consistent feature of all of the anomalous y-globulin groups.In the course of immunochemical studies of y-globulins, differences were observed in the antigenic composition of S pieces obtained by papain digestion of individual myeloma proteins (25,26).In view of previous observations (16,27,28) that the antigenic determinants common to all y-globulin groups were present in the S pieces from y-globulin molecules and that Bence Jones proteins were antigenically related to the S pieces, studies were undertaken to determine whether all four classes of proteins formed in malignant plasma cells could be divided into two groups on the basis of readily identifiable antigenic differences.Two forms of molecules (types I and II) differing in antigenic composition were identified in each anomalous protein group (29). Further studies demonstrated that two sets of antigenic determinants (types I and II) were common to all the y-globulin groups, but that the relative frequency...