Objectives - The humoral immune response seems to play a role in the pathogenesis of multiple sclerosis (MS). The blood-brain-barrier (BBB) and particularly the endothelial cell may be a possible target for this immunoresponse. Material and methods - Using an ELISA technique, we have investigated the prevalence of antibodies directed against human vein endothelial cells in the sera of 84 patients with MS, 35 stroke patients, 50 systemic lupus erythematosus (SLE) and 76 normal controls. The measurements in MS patients were tested a second time after cytokine stimulation with gamma and beta-interferon at different doses. Seven MS patients (two positive and five negative) had three or more-clinical assessments including the Expanded Disability Status Scale (EDSS) over a three-month period, and at least three AECA determinations were carried out. Gadolinium MRI examinations were performed monthly during these three months. Results - anti-endothelial cell antibodies (AECA) have been identified in 9 of 84 patients suffering from MS (10.71%), in 3 of 35 stroke patients (8.57%) and in 20 of 50 SLE patients (40%). None of 76 normal controls had a positive titre of AECA. Cytokine stimulations did not modify the detection of these antibodies. No correlation between AECA and different clinical parameters such as onset age, clinical symptoms at onset and at sampling, clinical course and score measured by the EDSS was found in MS patients. No relationship was found between MRI activity and the presence of AECA. Conclusion - AECA do not seem to be a marker for a specific subset of MS patients.