Continued studies of experimental allergic encephalomyelitis (EAE) will focus on several events and determinants discovered during the preceeding period of grant support and shown to be of special immunopathogenetic importance in this prototypic autoimmune disease: 1. The role of macrophages, in addition to lymphoid cells, in initiating and effecting immune responses of Lewis rats to myelin basic protein (MBP) and other antigenic constituents of central nervous system (CNS) tissue. 2. Interrelationships between the clotting cascade, CNS fibrin deposits associated with edema formation, and enzymatic degradation of MBP in development of EAE in Lewis rats. 3. Identification and characterization of the MBP-reactive moiety in cell-free supernatants derived from sensitized lymphoid cells of Lewis donor rats which endow such supernatants with EAE transfer activity. 4. Mode of action of a serum and cerebrospinal fluid (CSF) factor indistinguishable from MBP in its antibody binding capacity, designated as MBP-SF and MBP-CSFF, which appears to have an immunoregulatory role in development of EAE in Lewis rats. 5. Gene-specified cellular and/or humoral factors responsible for the extraordinary insusceptibility of Brown Norway rats to EAE. 6. EAE potentiating effect of total body irradiation of sensitized hamsters.