Rheumatoid factors (RFs) are present in a wide spectrum of diseases, but the diversity of these antibodies may vary greatly according to the underlying disease process. To analyze the diversity of these molecules, we have recently developed in the Scripps laboratory three cross-reactive idiotypic reagents against human monoclonal rheumatoid factors. These reagents detect unique markers associated with the kappa light chain variable region of the antigen binding site of these molecules. We have characterized the expression of the three crossreactive idiotypes in serum RFs of patients with rheumatoid arthritis, Sjogren's syndrome, and seropositive elderly. The autoantibodies from Sjogren's syndrome patients and from normal patients were restricted in heterogeneity and frequently displayed two or more of the crossreactive idiotypes. In contrast, the RFs from rheumatoid arthritis patients expressed only one of the three cross-reactive idiotypic markers, suggesting greater structural diversity. The presence of shared idiotypes implies a common origin of the light chains from a single light chain gene or closely related genes. Crossreactive idiotypes are useful diagnostic tools that distinguish the rheumatoid factors from different clinical processes and may provide insights concerning disease pathogenesis.