Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human autoimmune central nervous system (CNS) disease multiple sclerosis (MS). To examine the role of B cells in EAE with a relapsing and remitting disease course (R-EAE) we generated (B10.PL×SJL/J)F1 mice deficient in B cells by disrupting their μ heavy chain transmembrane region (B10.PL×SJL/J)F1μMT^−/−. By immunizing (B10.PL×SJL/J)F1 and (B10.PL×SJL/J)F1μMT^−/−mice with the encephalitogenic N-terminal peptide Acl-11 of myelin basic protein (MBP), we observed that B-cell deficient mice exhibited a relapsing and remitting disease course. Since a similar day of onset and day of first relapse were observed these data suggest that B cells do not play a vital role in the activation of T cells leading to the initiation of EAE, nor in the reactivation of T cells resulting in R-EAE.