Von Willebrand factor (vWf:Ag) is an important product of endothelial cells whose major known functions are coagulation and platelet adhesion. It appears to behave as an acute-phase reactant, levels being elevated in the plasma in a wide variety of inflammatory disorders and in the extravascular compartment in at least some of them. To determine if products of mononuclear cells, activated as part of these disease processes, may directly influence the synthesis and or release of this substance, confluent human umbilical vein endothelial cells were cultured in the presence of supernatants of mononuclear cells undergoing a mixed lymphocyte reaction, and a variety of other purified or recombinant mediators including interleukin-1 (IL-1), interleukin-2, gamma-interferon and prostaglandin E2. The endothelial cell supernatants were then assayed for vWf:Ag levels using a sensitive enzyme-linked immunoassay. The results of this study demonstrate that supernatants of a mixed lymphocyte reaction increase the synthesis and or release of vWf:Ag from endothelial cells in culture by about 100-150%. As these supernatants did not cause any increase in the release of radioisotope from 51Cr-labeled endothelial cells, it appears very unlikely that this increase was simply due to the passive release of this material from dead and dying cells. Increased vWf:Ag release was also demonstrable with purified IL-1 but not with any of the other mediators tested. These results suggest that IL-1 is able to increase the release of vWf:Ag from endothelial cells largely by an increase in synthesis and indicate at least one mechanism whereby mononuclear cells, activated during the course of an inflammatory response, may be able to influence coagulation and platelet function.