Rabbits immunized with monkey encephalitogenic protein (EP) complexed to deoxyribonucleic acid (DNA) formed complement-fixing antibodies that reacted well with EP from monkey, bovine, and human brain and the large EP of rat brain. Reactivity with the small EP of rat brain was much less. The antibodies, analyzed by the quantitative micro-complement fixation test, were of the 7S class, were produced in high titer, and failed to react with histone, lysozyme, or acidic liver extracts. Immunohistochemical studies revealed that the antibodies bound to central nervous system white matter from human, rat, guinea pig, and mouse as well as human peripheral nerve myelin. These findings demonstrate that the immunogenicity of EP is greatly enhanced by attachment to DNA and perhaps other negatively charged molecules. This method makes available anti-EP with which to investigate immunochemically the antigenic and conformational features of EP.