OBJECTIVES: To evaluate the diagnostic and pathogenetic significance of IgA rheumatoid factor (RF) subclasses in rheumatoid arthritis (RA). METHODS: Rheumatoid factors of the IgA class and IgA1 and IgA2 subclasses were measured by enzyme linked immunosorbent assay in 58 patients with RA, 31 patients with other rheumatic diseases, 30 non-rheumatic individuals with increased concentrations of IgA RF, and in 100 randomly selected healthy controls. RESULTS: Using a 95% cut off for the controls, 55% of the RA patients had increased total IgA RF, 64% IgA1 RF, and 60% IgA2 RF. RA patients with extraarticular manifestations more often had increased concentrations of IgA RF and both subclasses than patients without such manifestations (p < or = 0.01). Nearly all (31/32) RA patients with increased IgA RF had increases in both IgA RF subclasses, compared with 67% (20/30 of nonrheumatic symptom free individuals with increased IgA RF (p = 0.002). CONCLUSION: Increased concentrations of the IgA2 RF subclass appears to be more specific for RA than increased IgA1 RF. Measurement of IgA RF subclasses may be clinically useful.