The size of B-cell subsets appears to be under genetic control, but the mechanism of this regulation is unknown. By analyzing five congenic strains of mice that differ only in their H2 haplotype, we addressed the issue of whether the MHC genes are involved in the relative proportions of B-1a, B-1b and B-2 cells. Not only were there considerable differences in the percentages of B-1 in B cells between H2s mice which were the highest [78.5+/-0.8% in the peritoneal cavity (PerC), and 26.3+/-0.5% in the spleen] and H2d mice, which were the lowest (15.2+/-0.6% in the PerC, and 10.9+/-0.6% in the spleen), but the percentages of B-1a cells varied inversely to those of B-1. Crosses between H2s and H2d strains showed that the highest B-1 frequencies occurred in F2 progeny expressing the homozygous H2s (70.8+/-2.1% in the PerC, and 30.0+/-0.5 in the spleen), and the lowest in that expressing the homozygous H2d haplotype (8.9+/-0.6% in the PerC, and 8.6+/-0.4% in the spleen). A dose effect of H2 was established in heterozygous F1 and F2 mice. As mice aged, there was a reduction of B-1 cells in the PerC, at the expense of B-1b in the H2s, but not in the H2d mice. Hence, the H2 genes appear to participate in regulating the proportions of B-1a, B-1b and B-2 cells.