Sjogren's syndrome presents a wide spectrum of disease manifestations ranging from benign to malignant lymphoproliferation. Sera from 21 patients with primary Sjogren's syndrome, 63 patients with other autoimmune rheumatic diseases, and 140 normal controls were studied by using high-resolution gel electrophoresis combined with immunofixation and specific absorption studies. Two-thirds of the sera from Sjogren's syndrome patients contained free monoclonal lambda light chains. In addition, one patient with Sjogren's syndrome and pseudolymphoma had a circulating monoclonal IgM-lambda immunoglobulin. In contrast, only 16% of the patients with other autoimmune diseases and 5% of normals had monoclonal bands; none of the other patients studied exhibited monoclonal-free lambda light chains in their serum. Our findings suggest that the monoclonal process in Sjogren's syndrome starts early in the disease process in a subset of B cells.