Fibrinolytic parameters and von Willebrand factor (vWF) antigen were measured in the plasma of 10 patients with hemolytic uremic syndrome (HUS). Samples were taken at presentation and again 2 wk later, before and after infusion of 1-desamino-8-arginine vasopressin. Compared with the plasma values of healthy control children, levels of tissue-plasminogen activator (t-PA) antigen, plasminogen activator inhibitor type I (PAI-1) activity, and vWF as well as fibrin(ogen) degradation products were significantly elevated in the plasma of HUS patients on admission. No response of the fibrinolytic parameters and vWF were seen when 1-desamino-8-arginine vasopressin infusion was given on admission. After 2 wk, t-PA antigen and vWF had partially returned to basal values, and t-PA antigen increased rapidly again after 1- desamino-8-arginine vasopressin infusion. To investigate whether verocytotoxin contributes to the alteration of the fibrinolytic system found in HUS patients, purified verocytotoxin-1 (VT-1) was added to the media of cultured human endothelial cells. Addition of VT-1 alone did not change the production of t-PA, plasminogen activator inhibitor type I, and vWF antigen in these cells. However, when the endothelial cells were preincubated with tumor necrosis factor-α to increase the number of VT-1 receptors, VT-1 induced a marked decrease of the synthesis of t-PA, plasminogen activator inhibitor type I, and vWF. This was caused by a decrease in overall protein synthesis in the tumor necrosis factor-α- and VT-1-treated endothelial cells. We conclude from this study that the systemic fibrinolytic parameters measured in the plasma of HUS patients are probably not a direct effect of VT-1 on the endothelium but are sequelae of the disease in which the intestine and the kidney are predominantly affected. Chemicals/CAS: argipressin[1 deamino], 113-81-5; plasminogen activator inhibitor 1, 140208-23-7; tissue plasminogen activator, 105913-11-9; verotoxin, 108066-86-0; von Willebrand factor, 109319-16-6; Bacterial Toxins; Desmopressin, 16679-58-6; Fibrin Fibrinogen Degradation Products; Plasminogen Activator Inhibitor 1; Shiga-Like Toxin I; Tissue Plasminogen Activator, EC 3.4.21.68; Tumor Necrosis Factor; von Willebrand Factor