Activated cerebral vascular endothelial cells express leukocyte, vascular cell, and intracellular adhesion molecules (E-selectin, VCAM-1 and ICAM-1) which facilitate leukocyte adhesion to endothelium and migration into inflammatory lesions. Paired serum and cerebrospinal fluid (CSF) levels of soluble (s) E-selectin, sVCAM-1 and sICAM-1 were determined by ELISA in patients with clinically definite MS in relapse, and patients with other inflammatory (IND) and non-inflammatory neurological disease (NIND). CSF levels of sVCAM-1 and sICAM-1 were significantly increased in MS patients compared to IND and NIND patients. Elevation of CSF sVCAM-1 in MS patients was the most marked finding (P = 0.0001) and an increased sVCAM-1 index indicated that this was due to intrathecal release of sVCAM-1. There were no differences in serum and CSF sE-selectin levels between the study groups. Measurement of the sVCAM-1 index may provide a marker of disease activity in patients with clinically definite MS.