In this study we describe for the first time the production of stable human B cell lines and clones that secrete IgM antibody specific for human myelin basic protein. The technique based on limiting dilutions of Epstein-Barr virus (EBV)-transformed peripheral B cells from patients with multiple sclerosis precluded the need for preselecting or stimulating antigen-specific B cells. Most of the cell lines were stable for at least 6 months in continuous culture and produced 5-12 micrograms/ml antibody after 2 weeks in culture. The myelin basic protein (MBP)-specific B cells were surface IgM positive, and occurred with a frequency of approximately 1/2500 mononuclear cells in peripheral blood. The successful selection and quantitation of specific B cell clones described here suggests that this technique is well suited for evaluating B cell responses to known and suspected antigens and autoantigens.