Publisher Summary This chapter discusses experimental autoimmunity using experimental allergic encephalomyelitis as a prototype. This experimental disease makes possible a firsthand presentation both of its well-established facets, such as the production of the disease and the source and character of the antigen, and also of the still outstanding questions relating to the nature of the immunological mechanisms that produce the pathological lesions. There is reason to believe that experimental autoimmune diseases of the type discussed in this chapter represent promising model systems for probing an enormous array of questions and problems. It ranges from clinical areas into the heart of cellular biology. There is a clear need not to discover more models and new experimental diseases but to find new information and meaning within the ones close at hand and awaiting further dissection. Freund's adjuvant, the isolation and characterization of the tissue antigens, and the interplay of sensitized cell and antibody and their combination with antigenic determinants are some of the issues awaiting intensive investigation. The characterization and localization of encephalitogenic antigen; transfer of allergic encephalomyelitis to lymphoid cells; “target systems” for study of cytotoxic antibrain antibodies, complement-fixing antibodies, and protection against allergic encephalomyelitis; and modification and prevention of allergic encephalomyelitis are also discussed in the chapter.