OBJECTIVE Rheumatoid factors (RFs) in sera from rheumatoid arthritis (RA) patients bind better to agalactosyl IgG [gal(-) IgG] than to native IgG. Recently, a novel lectin-enzyme immunoassay (LEIA) which can detect all isotypes of the immunoglobulins was developed in Japan. Since RFs are also detectable in Sjögren's syndrome (SS), we determined anti-gal(-) IgG antibodies and RF isotypes in sera from primary or secondary SS and RA patients to elucidate the clinical significance of these antibody profiles. METHODS A series of 128 patients with primary SS (35 pts.), RA (57 pts.), or secondary SS [n = 36 pts., the SS being associated with RA (RA-SS) in 12 pts., systemic lupus erythematosus (SLE-SS) in 17 pts., and mixed connective tissue disease (MCTD-SS) in 7 pts.] and 38 healthy females were examined. Anti-gal(-) IgG antibodies were measured with a LEIA kit (ED055) using human gal(-) IgG as antigen. IgG-, IgA- and IgM-RF were determined with an enzyme-linked immunosorbent assay kit using human IgG-Fc as antigen. RFs were also examined by a conventional assay (laser nephelometry; LN-RF). RESULTS Serum anti-gal(-) IgG antibody titers were higher in RA than in primary SS, SLE-SS or MCTD-SS, but the incidence of the antibodies did not differ between RA and primary SS. In both RA and primary SS, the antibodies were positive in half of the LN-RF-negative patients, and were also detected in almost all of those patients who had at least one of the RF isotypes. LN-RF, IgG-RF, IgA-RF and IgM-RF were present more frequently and their titers were higher in RA than in primary SS, but IgA-RF levels were similar in both groups. In RA-SS, all of the antibody titers were notably higher than in RA or primary SS. In RA and primary SS, IgA-RF and IgM-RF were common RF isotypes, and anti-gal(-) IgG antibody levels correlated well with LN-RF, IgA-RF and IgM-RF levels. These antibody profiles did not relate to any of the clinical parameters in RA, but all the antibody titers correlated with anti-SS-A/Ro antibody levels in primary SS. CONCLUSIONS The anti-gal(-) IgG antibodies are not specific for RA; they are also frequent in SS. Our LEIA for antibodies is a very sensitive method to detect all RF isotypes in both RA and SS. Most of the antibody profiles are common to both diseases, although antibody titers are higher in RA, especially in RA-SS.