IgG subclass deficiency was recognized as a separate disease entity in the early seventies and was shown to be associated with an increased susceptibility to infections. Although deletions of the corresponding gamma genes have been demonstrated in a few cases, a majority of patients suffer from a regulatory dysfunction, and the deficiencies are most often relative rather than absolute. Some of the molecular mechanisms underlying the disorder have been unraveled recently. In this review we will touch upon the deletions described within the IGHC locus but mainly concentrate on the regulatory aberrations involved in IgG subclass deficiency.