Rheumatoid factors (FRs) are auto antibodies which react with different antigenic sites on the Fc piece of human IgG. They appear in large amounts in serum and synovial fluid of patients with rheumatoid arthritis (RA) but they are not specific to this disease. Different methods of detection have been proposed but they induce a low threshold of sensibility and regularly give rise to a low specificity for RA diagnosis. Those auto antibodies have a weak affinity for their antigen. However, despite this weak affinity, they contribute to the formation of large and stable articular immune complexes which could induce inflammatory synovial processes during RA. Occurrence of RFs during various infectious diseases is an argument for a protective role of RFs. This protective role is supported by the findings that RFs structural genes are largely distributed in normal populations and, in part, inherited, and that normal peripheral blood lymphocytes are able to make IgM FR when in vitro polyclonally stimulated.