A study has been made of the presence of the major rheumatoid Factor cross-reacting idiotype (RCRI) in the serum of patients with seropositive and seronegative rheumatoid arthritis as well as in the cytoplasm of plasmacells induced by cultivation of peripheral blood leucocytes (PBL) from the same RA patients and from normal humans. The PBL were stimulated in vitro with two different B cell mitogens, namely pokeweed mitogen (PWM) or Staph Auerus Cowan strain I (SAC). The RCRI was detected in the serum of seropositive RA patients and in the serum of four out of twenty seronegative RA patients. In these four, however, the seronegative condition was only apparent, since all four had hidden rheumatoid factors that could be shown after dissociation from IgG. The expression of the RCRI in the cytoplasm of PWM-stimulated PBL from seronegative RA patients was concordant with the expression in the serum. Thus the majority of truly seronegative RA patients also appear not to express the RCRI neither in the serum nor in the cytoplasm of plasmacells induced by PWM stimulation of PBL. An unexpected finding was the detection of the RCRI in plasmacells obtained by SAC stimulation of PBL from normal individuals. Up to 40% of RCRI-positive plasmacells were seen in many of these cultures, as opposed to an average of 2% in cultures stimulated with PWM from PBL of the same individuals. High percentages of RCRI-positive plasma-cells have previously been detected by us in PWM cultures only if these were from PBL from RA patients. Our working hypothesis is that PWM is a non-selective stimulator of B cells and that RCRI + precursors are in high frequency in RA patients, whereas SAC selectively stimulates these precursors even in normal PBL populations, where their frequency is not abnormally high.