Two patients with 47,XXX karyotypes and premature ovarian failure are described. Both presented with episodes of amenorrhea, elevated levels of circulating follicle-stimulating hormone and luteinizing hormone, and decreased estrogen concentrations. However, evidence of follicular activity existed in both cases. Why some women with 47,XXX karyotypes suffer from premature ovarian failure and why others have normal fertility and normal lengths of reproductive function is not known. Reports of immunologic disorders in patients with the triple-X syndrome and data showing that control of the lymphocyte may be related to the X chromosome point to a possible link between premature ovarian failure in 47,XXX women and immunologic abnormalities.