Background: Genetic susceptibility to common variable immunodeficiency (CVID) has been linked to the inheritance of part or all of 2 extended major histocompatibility complex haplotypes: HLA*B8*DR3(17) and HLA*B44*DR7. Objective: To determine whether the inheritance of these major histocompatibility complex susceptibility haplotypes correlates with absolute B-cell numbers. Methods: A retrospective medical record review of 55 consecutive patients with CVID whose blood was analyzed for B-cell numbers using a fluorescent-activated cell sorter. Results: The mean ± SD absolute count of CD19+ B cells among the 36 patients (65%) with CVID who had inherited HLA*B8 or HLA*B44 was 218 ± 23 cells/mm3 compared with 119 ± 27 cells/mm3 in those who had not inherited HLA*B8 or HLA*B44 (P = .008). There were no significant differences in B-cell numbers among the 33 patients (60%) with CVID who had inherited HLA*DR7 or HLA*DR3(17) and those who had not. Conclusions: Patients with CVID who inherited HLA*B44 or HLA*B8 tended to have higher numbers of B cells in the blood than those who did not, suggesting that the mechanism of immunodeficiency may differ.