Objective. To evaluate the possibility that lymphoproliferation in primary Sjogren's syndrome (SS) arises within a subset of B cells.Methods. A panel of monoclonal antibodies (MAb) specific for rheumatoid factor (RF)-associated cross-reactive idiotypes (CRI) and anti-V, and anti-V, subgroup antibodies were used to define the clonality of B lymphocytes undergoing neoplastic transformation in 5 patients with primary SS. Anti-CRI antibodies were also used to study longitudinal variations in serum paraprotein levels and in vitro regulation of IgM and IgM-RF production by peripheral blood lymphocytes. in serum and culture supernatants by enzyme-linked immunosorbent assay. Heavy and light chain isotypes and V, subgroups of the paraproteins were determined by immunoelectrophoresis, immunofixation, and Western blotting.Results. Paraproteins from all patients expressed an epitope associated with VJIIb sub-subgroup of light chains. Three of the paraproteins were cryoglobulins with RF activity, all of which expressed the VJIIbassociated CRI (detected by MAb 17-109) and the V,I-associated CRI (detected by MAb G6 and GS). None of the paraproteins expressed the V,III-associated CRI (detected by MAb B6 and D12). The CRI were consistently expressed over a period of 5-6 years. The anti-CRI and anti-subgroup antibodies substantially inhibited spontaneous production of IgM-RF and IgM by peripheral blood B lymphocytes from 3 of the SS patients.