A major proportion of the cases falling into the categories of cerebral palsy and mental retardation are attributable to developmental brain disease. The etiology and mechanism of processes which result in these diseases are at present, largely unknown. Yet, the magnitude of the public health problem that these diseases produce in the human population is considerable. In an effort to study the possible role of hypersensitivity mechanisms in developmental brain disease we have undertaken studies of the sigma antigen which is found only in brain and thymus derived lymphocytes. We have thus far shown the theta content of peripheral theta bearing cells can be suppressed or depleted whereas the theta content of brain is unaffected. The histological studies as well show the changes in peripheral sigma bearing organs but no abnormality of brain. In our studies of the genetics of immune responsiveness conducted this year we have discovered an immune response gene which governs the ability of a rat to develop experimental allergic encephalomyelitis (EAE). This gene, a dominant, is on the same chromosome as the gene which determines the major graft rejection antigen. We have in addition devised a specific immunotherapy for EAE on the basis of this gene. These findings are of great relevance to two common human diseases which very likely share the same disease mechanism as EAE, namely, Multiple Sclerosis and Acute disseminated encephalomyelitis. Similar principles may lead to a specific immunotherapy for these human diseases.