A therapy aimed at blocking the Fas/Fas ligand (FasL) system was investigated using a relapsing form of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Intracisternal administration of neutralizing antibody against Fast during the progression phase of EAE significantly reduced the severity of the disease with milder inflammation and myelin breakdown in the central nervous system (CNS). These results raised the possibility that the Fas/FasL system might contribute to tissue destruction in the CNS in the acute phase of EAE and that the intrathecal administration of neutralizing antibody against Fast may be beneficial for suppression of the acute phase of RIS.