AbstractRheumatoid factor (RF), i.e. a family of autoantibodies against the Fc part of IgG, is an important seromarker of rheumatoid arthritis (RA). Traditional particle agglutination without disclosing the antibody isotype remains the predominating diagnostic method in clinical routine. Although IgG‐RF attracts pathogenic interest, its detection remains technically challenging. The present study aimed at developing a set of tests identifying IgG‐RFs directed against the four IgG subclasses. IgG‐RF against either subclass of human IgG‐Fc were analysed with four novel enzyme‐linked immunosorbent assays (ELISAs) utilizing four recombinant human Fc‐gamma fragments (hIgG1–4) as sources of antigen. Sera from 40 patients with recent onset RA (20 seropositive and 20 seronegative by IgM‐RF and IgA‐RF‐isotype‐specific ELISA) were analysed. Sera from 20 healthy blood donors served as reference. Among the IgM‐/IgA‐RF‐positive RA‐sera, IgG‐RF was found directed against hIgG1 and hIgG2, but not against hIgG3 or hIgG4. Significant correlations were seen between IgG‐RF against hIgG2‐Fc and IgM‐RF (r = 0.666) levels. Further prospective studies are warranted to elucidate any correlation to disease course and outcome.