Serum inhibitory factors (SIF) have been demonstrated in several infectious diseases and autoimmune disorders. Most likely, they are caused by an immune reaction, and their persistence indicates a chronic course. Sera and synovial fluids of 31 patients with rheumatoid arthritis and of 33 patients with arthrosis were therefore studied, in order to determine whether immunosuppressive factors exist only in inflammatory diseases and whether their titers correlate with the activity of the disease. PHA-induced stimulation of normal peripheral blood lymphocytes, measured as 3H thymidine uptake, in the presence of patients' serum, was related to lymphocyte stimulation observed in the presence of control sera. Using the MIF-agarose assay, the effect of sera and synovial fluids on the tuberculin-induced migration inhibition was also studied. Sera of 27 of 31 patients with rheumatoid arthritis inhibited mitogen-induced normal lymphocyte thymidine uptake and abolsihed migration inhibition, probably by blocking MIF-production. High titers appeared to predict an unfavourable course. In contrast, sera of all 33 patients with degenerative joint disease failed to exert these effects. Synovial fluids of all patients, irrespective of the nature of the underlying joint disease, did not affect lymphocyte stimulation or leukocyte migration. Other factors, such as immune complexes, cytotoxic antibodies, or drug metabolites could be excluded as potential causes of the observed effects exerted by rheumatoid arthritis sera. These results indicate that the presence of serum factors inhibiting PHA-induced lymphocyte stimulation and leukocyte migration inhibition, respectively, may be used as a diagnostic tool in the differential diagnosis of rheumatoid arthritis.