The association between elevated serum rheumatoid factor and rheumatoid arthritis (RA) has been confirmed repeatedly and interpreted as strong evidence for an immunologic basis for the disease. In recent years, considerable additional evidence supporting this view has been obtained, strongly suggesting a role for CD4 + T cells in the pathogenesis of RA. An alternative view has also gained support, however. Based on studies of animal models and of RA itself, several lines of evidence have emerged that indicate that nonimmunologic pathways are operative in established RA. These observations have fostered the hypothesis that the evolution of RA may be associated with the emergence of non-T-cell-dependent autonomous pathways that dominate the latter stages of the disease.