Autosensitization to some central nervous system antigen still remains one of the best hypotheses for the continuing pathogenesis of multiple sclerosis (MS). Enough is now known about the cause, pathogenesis, and treatment of experimental allergic encephalomyelitis (EAE) to test this hypotesis. Reports of therapeutic failure of the encephalitogen myelin basic protein (BP) in the treatment of MS have their counterparts in similar therapeutic failures in EAE. Only highly inbred strain 13 guinea pigs respond much less well to simple BP therapy, and monkeys hardly at all. In both strains of monkeys so far studied, a nonspecific adjunctive factor–an antibiotic in Macaca mulatta and a steroid in Macaca fascicularis—is also required. Accordingly, human trials of the therapeutic efficacy of BP in MS should include its administration in large concentrations together with an adjunctive agent.