Studies have been described which delineate an unusual myeloma protein as a hybrid molecule consisting of heavy chains that are primarily IgG4 but with the C terminal homology region IgG2. The hybrid character of this protein was demonstrated mainly through the use of a wide variety of antigenic markers which have been localized to specific areas of the heavy chains of the different IgG subclasses. The highly purified myeloma protein contained three IgG4 markers but lacked two others that are found in all other Ig4 proteins. In addition it showed the presence of three IgG2 antigens but lacked five others that are characteristic of this subclass. The IgG4 markers which were present are all found in the CH1 and CH2 homology regions whereas the missing markers are in CH3. The reverse situation applied to the IgG2 antigens. These results indicated that the hybrid protein was made up of IgG4 in the CH1 and CH2 portion of the heavy chain and IgG2 in the CH3 area. Evidence was obtained for a normal counterpart to this protein in certain Negro sera but not in other populations; the myeloma protein was derived from a Negro. It appeared to represent a genetic variant in this population. The studies on this hybrid protein provided further data for the tentative order of the IgG subclass cistrons in the chromosome. Some indication was obtained for a possible duplication of the IgG2 gene at least in the Negro population.