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Rheumatoid arthritis an antigen-driven autoimmune disease and the eliciting antigens are unknown. They should be present in immune complexes of synovial fluids. The immune complexes were isolated from synovial fluids of patients with rheumatoid arthritis and analyzed by polyacrylamide gel electrophoresis and Western blotting. Immune complexes contained IgG as major protein. The antibodies dissociated at pH 2.5 and self-aggregated upon neutralization. In ELISA assays, they had the highest specificity to homologous IgG, less to normal IgG and lowest of heterologous arthritic IgG confirming earlier results that altered IgG structures were antigenic. Sequencing of the Fc-regions revealed mutations in all patients analyzed. Therefore, mutations within the Fc-regions of IgG could be antigens in rheumatoid arthritis. We propose that methods should be developed to prove this hypothesis.