Rheumatoid arthritis (RA) is associated with several autoantibodies specific enough to serve as diagnostic and prognostic markers. These include rheumatoid factor (RF), antikeratin antibody (AKA), antiperinuclear factor (APF), and anti-RA33. The first three, and possibly also anti-RA33, may precede the onset of clinical RA. The prevalence of positive test reactions depends on the period between taking the specimen and onset of disease; when the period is short, the prevalence is nearly the same as in established disease. Thus, RA has a long asymptomatic period with broadening immunological activity. The assays for AKA and APF (and possibly also for anti-RA33), compared with RF testing, yielded greater specificity rather than the ability to define any subgroup with particularly severe disease. Used together, the above marker antibodies may form a new and more enlightened basis for defining seropositive RA. It is commonly believed that genetically mediated immune response plays an important role in the initiation of RA. However, the role of the major histocompatibility complex antigens may be in modulation of the inflammatory reaction in a later phase.