In vitro patterns of IgM and IgM rheumatoid factor (RF) synthesis exhibited by peripheral blood B cells (MNL) obtained from healthy individuals as well as patients with seropositive and seronegative rheumatoid arthritis (RA) have been previously examined. The present study was performed in a group of patients with non-rheumatoid seronegative arthritis (SNA) in order to compare patterns of in vitro IgM and IgM RF synthesis to that previously observed with seropositive and seronegative RA. Eighteen patients with SNA (4 ankylosing spondylitis, 10 psoriatic arthritis, and 4 unclassified variant disease) were studied as well as 18 healthy adult controls. Spontaneous release of IgM RF by MNL was not observed in SNA or controls. In contrast, IgM RF was detected in pokeweed mitogen (PWM)-stimulated MNL culture supernatants from 9/18 SNA (mean±SD=17.0±9.9 ng/106 cells), and 10/18 normal controls (16.7±9.9 ng). Synthesis of IgM by PWM-stimulated MNL from SNA (2 062±1 200 ng) was significantly less than observed with MNL from controls (4 093±1 896 ng) (P<0.001). There were no differences among the various SNA subsets with regards to the levels of IgM and IgM RF produced either spontaneously or after PWM stimulation. IgM RF constituted a small fraction of the total IgM in SNA and normals (0.9% and 0.5%, respectively). This is clearly distinct from seropositive RA in which we have previously established that IgM RF constitutes a substantial fraction of the total IgM (10.7%) (P<0.01). IgM and IgM RF production did not appear to be significantly influenced by immunosuppressive medication. The results suggest that regulatory mechanisms governing the expression of RF are intact in patients with SNA and that lack of in vivo RF production in these patients cannot be related to an absolute deficiency of PWM-inducible mature RF committed B cells. © 1984 Springer-Verlag.