NZB mice produce numerous autoantibodies and have a subpopulation of B cells characterized by marked spontaneous hypersecretion of IgM. The latter trait is determined by autosomal genes, in F1 hybrids of NZB and normal strains. We tested the hypothesis that the hypersecreting B cells of NZB mice are contained within a specific subpopulation by examining (CBA/N X NZB)F1 hybrids. CBA/N mice have an X-linked recessive defect that results in the absence of a functionally distinct B cell subpopulation and impaired antibody responses. The hyperactivity of B cells, characteristic of the NZB parent, was transmitted to the F1 female, but was not expressed by the F1 male, which manifested the CBA/N B cell hyporesponsiveness. By contrast, the NZB xenotropic virus was expressed equally by both male and female F1 mice. We conclude that the NZB B cell abnormality resides within the B cell subpopulation affected by the CBA/N mutation.