Several proteases have been implicated in regulating the turnover of mesangial matrix within the glomerulus. One such group, the plasminogen activators (PAs) and their inhibitor, PA inhibitor type-1 (PAI-1), is produced by glomerular cells with altered expression during nephritis. We report the effect of IL-1 and transforming growth factor-beta (TGF-beta) and a combination of the two cytokines on the secretion of tissue-type PA (t-PA) and PAI-1 from human mesangial cells. IL-1 significantly downregulates PAI-1 production and upregulates t-PA over a range of concentrations (1-10 U/ml), while TGF-beta (0.5-10 ng/ml) has the opposite effect. The combined effect of these factors is that TGF-beta attenuates the increase in t-PA and decrease in PAI-1 expression caused by IL-1, and has a dominant effect upon their secretion, thus decreasing t-PA and increasing PAI-1. These findings contribute to our understanding of fibrinolysis and tissue remodelling within the glomerular mesangium during the course of nephritis.