Rheumatoid arthritis (RA) is an autoimmune disease whose diagnosis was long based solely upon the demonstration of rheumatoid factors (RF) which are IgM antibodies with anti-IgG specificity. The development of modern techniques which are more sensitive and/or detect non-IgM rheumatoid factors has reduced the percentage of presumptive seronegative RA. Immunological studies of the disease also reveal other evidences of polyclonal B-lymphocyte activation: hypergammaglobulinemia, high levels of beta-2-microglobulin and circulating immune complexes, presence of various autoantibodies (anti-collagen, antilymphocyte and, in some instances, anti-nuclear antibodies). These anomalies are found, not only in the blood, but above all in the synovial fluid, which explains the low synovial complement level. The disturbances of cellular immunity cannot yet be used for diagnostic purposes, but suggest that the physiopathologic mechanism of RA involves a decreased T-suppressor lymphocyte activity and/or B-cell unresponsiveness to suppressor influences.