The relative contributions of CD5+ and CD5- B-cells in production of rheumatoid factors (RF) was evaluated in polyclonally activated B-cells from patients with IgA nephropathy (IgAN), rheumatoid arthritis (RA) and Graves' disease (GD). In IgAN and RA, diseases in which RFs are believed to be involved in pathogenesis, there were 10- and 4-fold decreases respectively in CD5+ IgG-RF-secreting B-cells compared with controls. Furthermore, the number of CD5- IgG-RF- and IgA-RF-secreting B-cells were increased 12- and 14-fold in IgAN and 9- and 4-fold in RA. Such abnormalities were not apparent in GD, in which RFs have not been implicated in pathogenesis. These findings are compatible with the concept of CD5+ RF-secreting B-cells normally acting to prevent production of potentially pathogenic RFs by CD5- B-cells. When IgAN or RA patients' B-cells were activated in the presence of control instead of autologous CD4+ cells, numbers of RF-secreting CD5- B-cells were reduced to the levels seen with control B-cells plus control T-helper cells. Presumably lymphokine secretion profiles of T-helper cells would be important in determining whether CD5+ or CD5- B-cells are activated to secrete RFs, and perhaps therapeutic manipulation of these profiles could restore normal activity of CD5+ B-cells in IgAN and RA.