To evaluate the activation of endothelial cells of the brain and the spinal cord, we investigated the presence of soluble endothelial leukocyte adhesion molecule-1 (sE-selectin) in the serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and those with human T-lymphotropic virus type 1-associated myelopathy (HAM). There were significantly higher levels of sE-selectin found in the serum of patients with relapsing-remitting MS during an exacerbation (p < 0.001) and those with chronic progressive MS (p < 0.01) compared with controls. Serum levels of sE-selectin in patients with HAM did not differ significantly from serum levels in controls or non-HAM carriers. We also found sE-selectin in the CSF of eight patients during an exacerbation of relapsing-remitting MS. These results suggest that an active immune reaction involving E-selectin production that is indicative of endothelial cell damage occurs in the CNS of patients during an exacerbation of relapsing-remitting MS. Thus, sE-selectin may be useful in monitoring disease activity in patients with relapsing-remitting MS.