Experimental allergic encephalomyelitis (EAE) is a well defined, reproducible entity based on sensitivity to autologous tissue antigen (for recent reviews, see references 1-3). Its importance as a model for certain forms of demyelinating disease in man has made it a subject of interest to investigators from a number of unrelated disciplines. However, immunologic and other investigations of the disease mechanism have been seriously handicapped by lack of information regarding the exact chemical nature of the encephalitogenic antigen or antigens in nervous tissue. The present paper presents for the first time precise chemical data regarding fractionated materials which show antigenic activity.The tissues of the central nervous system contain several distinct substances with the capacity to induce circulating antibody formation (4). Many of these substances, like the antigen(s) responsible for the production of EAE, are organ-rather than species-specific. Their exact chemical nature, however, even after 30 years of investigation, remains obscure. A few simple lipides have been reported to possess antigenicity even when produced synthetically. It is not known if any of these substances are encephalitogenic when administered with adjuvants, although some negative data have been obtained on this point (5).The earliest studies of EAE indicated that the encephalitogenie activity of nervous tissue is largely confined to those parts that axe rich in white matter (6, 7), and is absent from fetal or unmyelinated brain (7,8). As nervous tissue of foreign species is effective in producing EAE (7-11) the antigenicity is said to be organ-specific rather than species-specific. It has been reported that activity is associated with