This proposal is designed to develop information on the mechanism of demyelination that has been triggered by an immunological process, as in multiple sclerosis. Since, there is suggestive evidence for complement involvement in demyelination, we want to study: (1) how the myelin membrane interacts with the terminal complement proteins (membrane attack components) and (2) how the efficiency of membrane damage by complement can be modulated either positively or negatively. For the studies on complement-myelin interaction, we will use a tissue culture system with the neonatal mouse brain or spinal cord. For the studies on membrane modulation, we will use sheep erythrocytes and liposomes made with myelin lipid. There is also suggestive evidence that cytotoxic lymphocytes can attack myelin. Since there are many similarities between the membrane damage by complement and that mediated by lymphocytes, we believe that information developed in the proposed study will also be relevant to demyelination processes mediated by cytotoxic lymphocytes.