HLA class II antigens and the LFA-1 (lymphocyte function-associated type 1) glycoprotein family are cell surface structures of central importance in many lymphocyte reactions. Specific antibodies are normally restricted to particular IgG subclasses. In order to study the mechanism of isotype restriction we have analysed specific IgG1, IgG2, IgG3 and IgG4 antibodies directed against a number of different protein and polysaccharide antigens in individuals with HLA class II or LFA-1 deficiency. HLA class II deficiency resulted in decreased total IgG2, IgG4 and IgA in 4/4 patients, whereas total IgM and IgG were low in 2/4. In HLA class II deficiency the levels of specific antibodies directed against protein as well as polysaccharide antigens were frequently low. Virtually normal total as well as specific antibody levels were found in individuals with both severe and moderate forms of LFA-1 deficiency. There was no clear evidence for an abnormal subclass pattern of specific antibodies with a shift from one subclass to an isotype which is normally not used, in any of the patient groups investigated.