Over the past four decades, many patients have been reported to have deficiencies of one or more subclasses of immunoglobulin G (IgG), despite normal total IgG serum concentrations. However, except for those with extremely low or absent IgG2 concentrations and an inability to produce antibodies to polysaccharide antigens, it is difficult to know the true biologic significance of the many reported IgG subclass deficiencies. Completely asymptomatic individuals who totally lack IgG1, IgG2, IgG4, or IgA1 because of heavy-chain gene deletions have been described as producing antibodies normally. In addition, numerous healthy children who have low levels of IgG2 but normal responses to polysaccharide antigens when immunized have been similarly described. From these observations, it can be concluded that IgG subclass measurement is not very helpful in the general assessment of immune function. Such assays provide no information about the patient's capacity to produce specific antibodies to protein, polysaccharide, or viral antigens.