To investigate the role of thrombomodulin (TM) and tumor necrosis factor-α (TNF-α ) in hemolytic uremic syndrome (HUS), serum and urinary levels of TM and TNF-α were determined in patients with hemorrhagic enterocolitis (HC) of enterohemorrhagic E. coli O157: H7 infection. These patients were divided into two groups: an HUS group consisting of patients with HUS; an HC group consisting of patients without HUS. In the 10 days after the onset of diarrhea, the serum TM and TNF-α levels in the HUS group were significantly elevated compared with those in the control group but decreased after 11 days. The serum TM and TNF-α levels in the HC group were not elevated compared with those in the control group except for one case of TNF-α. It is suggested that the serum TM elevation showed the severity of endothelial cell damage. Urinary TM and TNF-α levels in the HUS group were significantly elevated in the first 10 days. The urinary TNF-α levels rapidly decreased after 11 days, while the urinary TM levels were persistently high. From these results, the sustained elevation of the urinary TM levels suggested the persistent presence of renal endothelial cell damage, and the decrement of urinary TNF-α levels suggested that TNF-α acted as a trigger of the renal endothelial cell damage in the first 10 days.