IgG subclasses represent distinct immunoglobulin types, each defined by unique primary structures of the constant region of the heavy-chain molecule, and each with characteristic biological and functional properties. New methods and reagents to measure serum concentrations have contributed to the study of the ontogeny, antigen restriction, and deficiencies of IgG subclasses. Distinct clinical entities of single or multiple IgG subclass deficiencies have been identified and the efficacy of immunoglobulin replacement therapy has been demonstrated in several instances.