Recently, a new culture system has been devised which leads to activation, proliferation and differentiation into antibody secreting cells of at least 90% of human peripheral blood B-lymphocytes. The system uses mutant EL-4 thymoma cells of mouse origin for B cell activation and T cell/macrophage supernatant as source of cytokines (L. Wen et al., Eur. J. Immunol. 17, 887, 1987). By an ELISA system with Fc fragments as antigen and the F(ab)2 fragment of antibodies against human IgM labelled with alkaline phosphatase, we analysed the frequencies of B cells producing IgM-RFs. The mean frequency of IgM-RF producing cells in normal controls was 1/3100 (s.d. = 0.2 log; n = 5) of circulating B cells. In 2 patients with seropositive rheumatoid arthritis (RA) the frequencies were higher (1/492; 1/262), but in 2 other seropositive patients a normal (1/5540) or even a decreased (1/20000) frequency was observed. The possible relation between circulating and synovial RF producing B cells is currently being investigated.