Breakdown of the blood-brain barrier, which consists of endothelial cells, is implicated essential in the pathogenesis of multiple sclerosis (MS). To examine the endothelial cell damage, we determined the von Willebrand factor and thrombomodulin, markers for endothelial cell activation and/or injury, in the peripheral blood of patients with MS. The subjects were 26 patients with relapsing-remitting MS and 35 control subjects (mean age +/- standard deviation, 44.8 +/- 9.6 years). Patients with systemic vasculitis were excluded. The plasma activity of von Willebrand factor was significantly higher in patients with MS in the active phase (n = 23; 44.6 +/- 9.6 years) than in the age-matched controls. This suggests that von Willebrand factor could be a useful marker for evaluating the breakdown of blood-brain barrier resulting from endothelial damage in MS. In contrast, the serum level of thrombomodulin was not significantly different between patients with active MS and the controls. In MS patients (n = 15; 44.2 +/- 2.2 years), the plasma activity of von Willebrand factor was significantly lowered after immunosuppressive treatment. This suggests that von Willebrand factor could be used as a parameter for assessing the effect of treatment in MS.