Although total concentration of immunoglobulin G has been quantitated in the lower respiratory tract of humans, the contribution of the 4 subclass species of IgG to total recoverable IgG protein has not been assessed. We have developed sensitive, micro-ELISA assays specific for the individual subclasses and employed them to measure serum and local intrapulmonary levels of these proteins. We have compared lung lavage and serum concentrations of these proteins (relative to albumin) and also compared these immunoglobulins with IgA and IgE. The results of serum level measurements of subclass proteins are similar to results reported by others; IgG1 and IgG2 are present in lung lavage in concentrations similar to their serum concentration, serum and lavage levels are directly related, and IgG4 is increased in lavage compared with that in serum, suggesting increased local synthesis or accumulation of this protein within the lower respiratory tract. Local intrapulmonary concentrations of both IgA and IgE also are increased compared with those in their serum concentrations. Local IgG3 is variable, with some subjects having increased amounts compared with that in serum, whereas others have concentrations similar to those in serum. These data suggest a preferential accumulation of IgG4 in the lower respiratory tract. It is possible that IgG4, like IgA and IgE, plays a special role in the immune defense of the lung.