Although the familial occurrence of primary immunedeficiencies is not uncommon, the occurrence of immunedeficiencies among female family members is unusual. Most cases of familial immunedeficiencies occur in male siblings and usually obey an x-linked recessive mode of determination.Data are presented on two sisters with identical primary immunedeficiencies. One sister presented with recurrent otitis, pyoderma, and H. influenzae ventriculitis. The second sister presented with what appeared to be pauciarticular rheumatoid arthritis. Both sisters had identical findings of decreased concentrations of IgG and IgA, normal concentrations of IgM, deficient antibody production, and absent lymphoid follicles and germinal centers in their lymph nodes, in the presence of normal cell-mediated immunity. These data are consistent with the diagnosis of primary immunedeficiency with hyper-IgM (dysgammaglobulinemia, type I) appearing for the first time in sisters. Chromosomal analysis revealed both sisters to have normal female karyotypes and study of the family pedigree failed to reveal consanguinity. This immunedeficiency probably represents a previously undescribed autosomal recessive form of primary immunedeficiency with hyper-IgM.