We studied growth and differentiation of B lymphocytes of patients with juvenile rheumatoid arthritis (JRA) using B cell enriched populations. Mitogen stimulation led to similar proportionate increases in proliferation and immunoglobulin (Ig) secretion in cultures of patient and control lymphocytes. While there was no increase in proliferation, IgG secretion was increased in the absence of mitogen. Nonmitogen activated Ig synthesis could be reduced by replacing culture medium with fresh medium after 16-20 h in culture. It was partly reconstituted by addition of recombinant cytokines, interleukin (IL), IL-2, IL-4, or IL-6. Our results suggest there may be a population of B circulating B cells in patients with JRA and other rheumatic diseases which is sufficiently mature to differentiate and secrete Ig in response to cytokines alone.