There is growing evidence that implicates B lymphocytes and their products in the pathogenesis of multiple sclerosis (MS). A subpopulation of B lymphocytes expressing the CD5 antigen are involved in several autoimmune disorders through the release of autoantibodies. In this study, we used three-color flow cytometry to examine the expression of CD5 antigen on B lymphocytes from patients with relapsing-remitting MS, and correlated this expression with features of disease activity and circulating levels of autoantibodies against myelin basic protein. CD5 expression on B lymphocytes was significantly higher in patients with active MS when compared to patients with clinically stable MS or those with inflammatory or noninflammatory neurologic disorders. CD5(+) B lymphocytes from patients with active MS correlated significantly with the number of gadolinium-enhancing MRI lesions, and inversely with disease duration. The expression of CD5 on B lymphocytes in MS patients also correlated with circulating levels antibodies against myelin basic protein. Results presented here indicate that clinically active MS is associated with an expanded population of peripheral CD5(+) B lymphocytes.