The middle part of the heavy chain of IgG3 (hinge region) which covalently links the two gamma3 chains to each other, is about 4 times larger than the same region in the three other human IgG subclasses. This is probably due to a quadruplication of a 45-nucleotide DNA segment resulting in a gamma3 hinge region which is 62 amino acid residues long and consists of an NH2-terminal 17-residue segment followed by a 15-residue segment which is identically and consecutively repeated three times. The NH2-terminal 17-residue segment shows 70% homology with the repetitive 15-residue segment and appears to be the result of a small insertion and several point mutations of the same 45-nucleotide DNA stretch. Since this unit of repetition shows 60 to 70% homology with the hinge of the other IgG subclasses, it may represent the primitive IgG hinge.