OBJECTIVE The role of hydroxyl radical (OH) damaged Immunoglobulin G (IgG) in rheumatoid arthritis (RA) has been investigated. METHODS The study was hypothesized that oxidative by-products, like OH-damage IgG, help to initiate autoimmunity in RA. To test this hypothesis, IgG was modified by OH. Immunogenicity of native and modified IgG was probed by inducing polyclonal antibodies in rabbits. Autoantibodies from 77 RA sera were screened by direct binding and competition ELISA. RESULTS The OH caused extensive damage to IgG. The OH-IgG was found to be highly immunogenic in rabbits as compare to native IgG. High degree of specific binding by 72.7% RA sera autoantibodies towards OH-IgG was observed, in comparison to its native analogue (p<0.05). CONCLUSIONS The OH modification of IgG causes perturbations, resulting in the generation of neo-epitopes, and making it a potential immunogen. The IgG modified with the .OH may be one of the factors for the induction of circulating RA autoantibodies.