Cell-mediated immunity (CMI) to myelin components has been implicated in Multiple Sclerosis (MS) pathogenesis: two targets were suggested, Myelin Basic Protein with controversial results and, more recently, gangliosides. In order to investigate their possible involvement, we have performed Leukocyte Migration inhibition (LMI) tests in the presence of human brain gangliosides. Thirty nine MS patients (twenty four bcing“definite”, according to McDonald and Halliday's classification), twenty nine patients with Other Neurological Diseases (OND), thirty six patients with Inflammatory diseases (ID) and forty healthy controls were tested. MS patients wcrc divided into two groups, depending on the clinical stage of the disease.The mean migration inhibiton percentage of the MS-attack group was found to be significantly different from the four others (p<0.01) (24.4±16.2 versus 10.9±8.5 in MS without attack, 4.4±12.9 in OND. 3.9±13.9 in ID and 11.1±12.1 in healthy subjects). LMI to gangliosides is therefore significantly increased during the attack stage in MS. These results support the notion of a Delayed Type Hypersensitiv-ity to these glycolipids during the active stage of the disease.