Lewis rats were treated from day of birth with a rabbit anti-rat IgM antiserum. As adults these animals were found to have no detectable serum IgM and greatly reduced levels of IgG. They failed to respond to the B-cell mitogen LPS, or to make antibodies to sheep red blood cells (SRBC) or myelin basic protein (BP). These B-lymphocyte and immunoglobulin-deficient rats failed to develop clinical or histological evidence of EAE when sensitized with either whole spinal cord or purified BP. That some T-cell functions of these suppressed animals were not altered was seen by their ability to respond normally to PHA and to reject tissue allografts. The results would suggest that B-cell function (immunoglobulin-antibody production) is essential for the induction of EAE.