Peripheral blood mononuclear leukocytes (MNL) from 22 healthy adults were tested for their capacity to produce IgM rheumatoid factor (RF) in vitro in the presence and absence of pokeweed mitogen (PWM). In no instance was spontaneous elaboration of IgM RF observed. However, stimulation of MNL with PWM resulted in the induction of IgM RF synthesis in 10 out of 22 individuals. The IgM RF in these culture fluids constituted only a small fraction of the total IgM (mean ± 1 S.D. = 1.01 ± 1.08%). The lack of correlation of IgM RF with total IgM in these culture fluids argued against nonspecific absorption of non-RF IgM on the IgG substrate utilized in the assay. Furthermore, fractionation of supernatants containing IgM RF on Sephadex G-200 indicated the material to co-elute with polymeric IgM and to preferentially bind to Fc coated tubes as opposed to Fab or BSA-coated assay tubes. IgM RF production induced by PWM was dependent upon de novo protein synthesis and exhibited T cell dependence. The data indicate that B cells capable of synthesizing RF commonly occur in normal individuals but are not ordinarily activated.