The pathogenetic anti-erythrocyte autoantibody responses of NZB mice were characterized at the level of the autoantibody secreting B lymphocyte. Clonal heterogeneity was evaluated by reference to certain phenotypic expressions of immunoglobulin heavy chain constant and variable region genes. The anti-X autoantibody response appeared completely restricted to the NZB strain and was predominantly of IgG class. Specific anti-X B2 lymphocytes exhibited marked clonal diversity in regard to immunoglobulin class and heterogeneity of autoantibody affinity as determined by competitive plaque inhibition assays. The anti-HB autoantibody response, a genetically non-restricted response, was predominantly of IgM class; splenic anti-HB B2 lymphocytes also exhibited marked clonal diversity in respect to immunoglobulin class and binding affinity of the secreted autoantibody. Neither response exhibited a maturational increase in homogeneity similar to that observed in anti-sheep red cell responses by NZB mice. These data indicate that heterogeneous sets of B lymphocytes are recruited in these responses, an observation consistent with the concept that the immunogenesis of these pathogenetic autoimmune responses may be immunoregulatory in nature.