Transforming growth factor-/3 (TGFP) is a growth modulator that stimulates the growth of fibroblastic cells but inhibits the growth of cells of epithelial origin. TGFP also influences the production of extracellular matrix proteins, and of proteases and the type 1 plasminogen activator inhibitor (PAI-1) by cultured cells. TGFP appears also to have various immunoregulatory effects, suppressing both Tand B-cell activities. It has been proposed that it might increase the expression of interleukin-I (IL-1) mRNA in cultured human monocytes, thus potentiating immune functions. To analyze the role of TGFP in IL-I production we have now quantitated the effect of this factor on the production of biologically active IL-1 as well as IL-10 mRNA expression. The effect of TGFP on IL-1 production optimally activated with bacterial lipopolysaccharide (LPS) was also studied. It was found that IL-1 activity and mRNA levels were rapidly elevated by LPS but not by TGFP. Culture fluids from monocytes treated with TGFP alone or with TGFP plus LPS inhibited the proliferation of the test thymocytes. After gel fil- tration, the media from TGFP-treated cultures showed no activity in the molecular weight area of IL-1 (approx. 15 kD), while the supernatants from TGFP plus LPS-induced cells contained IL-1 activity in these fractions, the magnitude of which was, however, at the same level as in the culture fluids derived from cells stimulated with LPS alone. Thus our results show that the TGFP used was biologically active but they provide no evidence for TGFP in the regulation of IL-1 production in human monocytes.