Twenty human monoclonal antibodies with rheumatoid factor (RF) specificity were produced from fusions using B lymphocytes derived from the synovial tissue of two patients with rheumatoid arthritis (RA) and one with the polyarticular form of juvenile rheumatoid arthritis (JRA) (1). All the 20 monoclonal antibodies were IgM. Fourteen of these were classical RFs with specificity restricted to IgG, and included 12 kappa and 2 lambda proteins. When the fine specificity for IgG Fc determinants were investigated most of them showed the Ga specificity. In addition, 5 lambda and 1 kappa monoclonal RF antibodies showed polyreactivity and also reacted with various other antigens than IgG (1). The 14 monoreactive RFs were further studied for the expression of RF-related cross-reactive idiotypes (CRI) and variable heavy (VH) and light chain (VL) subgroups. Only four of the twelve kappa RFs expressed the V kappa III subgroup. Three of them belong to the V kappa IIIb sub-subgroup and expressed the CRI 17.109. One of these 3 clones in addition expressed the VH I associated CRI G6. Five other monoreactive RFs expressed either or both of the VH III associated CRI B6 and D12 (2). Using staphylococcal protein A (SPA) binding as well as Northern blotting techniques (2), studies indicated that 10 out of the 12 RFs studied expressed the VH III regions and 2 expressed the VH I region. These data, both for the heavy and light chains, indicated a different V gene usage by the RF derived from RA patients than by the RF M-components derived from patients with mixed cryoglobulinemia and Waldenström's macroglobulinemia but without RA.(ABSTRACT TRUNCATED AT 250 WORDS)