Multiple sclerosis is a relatively common inflammatory demyelinating disorder of the central nervous system which affects a young patient population causing great cumulative disability. It is believed to be of autoimmune and/or infectious etiology. A comprehensive clinical research program in multiple sclerosis interfaces with the research laboratory which utilizes recent recombinant DNA technologies to understand the basic mechanisms of this neurological disease. Novel cloning strategies are employed to construct brain cDNA expression libraries and characterize brain antigens against which the immune response in multiple sclerosis is directed. In parallel, the oligoclonal restriction of both the B-cell and T-cell autoimmune response is studied at the cellular and molecular level, to identify the repertoire of immunoglobulin and T-cell receptor genes relevant to this and other neuroimmunological disorders. The development of specific immunomodulatory therapies is the goal of our improved understanding of the pathogenesis of multiple sclerosis.