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We report the first specific human immunoglobulin subclass probe which was obtained by subcloning the gamma 3 hinge region. This specific γ 3 probe allowed us to identify with certainty the Cγ 3 gene on Southern genomic blots to describe the first Cγ 3 restriction fragment length polymorphism (EZZ γ 3 RF) and to show that an IgG3 selective deficiency previously described serologically was not due to a deletion of the C 3 gene. Such a probe should be particularly useful for screening libraries from individuals with IgG3 immunodeficiencies or presenting unusual Cγ 3 genes and consequently for studying the Cγ gene evolution. Immunoglobulin IgCH gene (Human) Gm allotype Restriction fragment length polymorphism Immunoglobulin G3 deficiency Hinge