Rheumatoid synovitis is characterized by increased activation and proliferation of synoviocytes, which are an important source of cytokines. The role of Interleukin 4 (IL-4) and IL-10 on the production of mediators of inflammation by rheumatoid synoviocytes was studied herein. While IL-4 weakly affected the spontaneous PGE2 production, it strongly inhibited its production when cells were stimulated with IL-1 beta and TNF-alpha. IL-4 decreased by 60% to 80% the spontaneous and the IL-1 beta or TNF-alpha induced synthesis of GM-CSF. In contrast, IL-4 enhanced the spontaneous (2.6-fold), and to a lower extent (1.3-1.8-fold), the cytokine stimulated production of IL-6. This induction was not due to a passive release of pre-synthesized IL-6, since IL-4 increased the level of IL-6 mRNA expression induced by IL-1 beta. The D50 was 5 U/ml of IL-4 for both the stimulation of IL-6 synthesis and the inhibition of GM-CSF production. Kinetic studies of the action of IL-4 revealed a rapid and sustained inhibition of GM-CSF production, and a late increase of IL-6 secretion. By contrast, IL-10 had no effect on the production of either IL-6 or GM-CSF by synoviocytes. Thus, by inhibiting synoviocyte proliferation and inhibiting their secretion of PGE2 and GM-CSF, IL-4 displays on synoviocytes a series of biological effects which complements its anti-inflammatory properties on monocytes.