IgG subclasses differ from one another both immunochemically and functionally. An isolated absence of a certain specific subclass may or may not be associated with disease. However, an absence of serum (IgG 4 as measured by a sensitive radioimmunoassay is usually, if not always, associated with severe recurrent pyogenic infections, usually of the respiratory tract. IgG 2 and IgG 4 deficiencies tend to occur together, often in association with deficiencies of immuno-globulin A (IgA) and/or immunoglobulin E (IgE). The properties of IgG 1 are similar to those of IgG 3 and those of IgG 2 appear to resemble those of IgG 4 in certain respects. Specific combined deficiencies tend to be associated with certain diseases. Some patients with deficiency of an immunoglobulin G (IgG) subclass appear able to compensate and to avoid clinical disease whereas others are not. Overlap zones exist in the lower ranges of serum concentrations in which both healthy and immunoincompetent subjects are found. It is important to consider the concentration of each IgG subclass present in a gamma globulin preparation or in plasma used for replacement therapy. If specific antibody deficiences exist, it may be critical that the preparation used for replacement contains goodly amounts of the missing antibodies.