Attempts to detect immune mediators in rheumatoid arthritis synovial fluids (RA-SF) by bioassays have yielded conflicting results, and so we analyzed the immune reactions occurring within rheumatoid joints using monospecific immunoassays for cytokines such as interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2) and gamma interferon (gamma-IFN). Furthermore, we examined the IL-2 inhibitors to clarify the immunoregulatory mechanism in the lesion. SF from active RA contained a significant amount of IL-1 beta and IL-2 but not gamma-IFN. In contrast IL-2 inhibitor activity was depressed in RA-SF regardless of clinical disease activity. Our results suggest that cytokine overproduction and deficiency of inhibitory signals may result in the overactivity of cytokines and the overactivity may participate in the joint lesions of RA.