Although the occurrence of selective deficiencies of serum IgG subclasses has been known for 20 years, the large body of data presently available was collected only recently owing to the use of performing monoclonal antibodies. IgG subclass deficiency is frequent, both as an apparently isolated defect (about one fourth of patients suffering otherwise unexplained repeated infections) and in association with a number of primary and required immunodeficiency states. This paper briefly reviews the methodological problems of serum IgG subclass measurement and data on subclass deficiency in a variety of clinical conditions.