Surface IgG expression of 29 cases of hairy cell leukemia (HCL) was assessed using IgG-subclass-specific monoclonal and F(ab)'2 polyclonal antibodies. A marked preference for the IgG3 subclass was found, as 16 of 19 IgG-positive HCL's expressed IgG3. In 10 cases, IgG3 was concurrently expressed with other heavy chains. No preferential IgG3 expression was observed in 11 IgG-positive non-Hodgkin's lymphomas. The marked predominance of IgG3 in HCL suggests a deviation in heavy chain class switching that may be related to the characteristically very low expression of LFA-1 and ICAM-1 molecules on hairy cells, and hence a defect in T-cell hairy cell interaction.