Each immunoglobulin G (IgG) subclass has unique physicochemical properties and, probably, unique functions. Each heavy chain is coded by a separate gene on chromosome 14. Deficient synthesis of a subclass may be associated with recurrent or chronic infections, the deficiency not being detected by measurements of levels of total serum IgG. Measurement of levels of IgG subclasses should be part of the work-up of patients who have frequent infections but have normal levels of major immunoglobulin classes. Deficiencies of IgA or IgE frequently coexist with deficiencies of IgG2 or IgG4. Patients with a subclass deficiency often benefit from replacement therapy with intramuscular or intravenous IgG or plasma from a donor free of hepatitis and HTLV-III viruses. It may be critical to provide IgG or plasma that is a good source of the missing immunoglobulin class or subclass. Sometimes it is necessary to administer a product with antibodies to the virus or bacteria responsible for a particular infection.