In premature ovarian failure, secondary amenorrhea with elevated gonadotropins usually occurs before the age of 40 years. The condition may be due to a known genetic disorder associated with rapid atresia of the follicles (Turner variants) or to the destruction of germ cells by viral infection, drugs, and other agencies. In addition, certain immune disorders, such as the presence of anti-ovarian antibodies and myasthenia gravis, are known to produce premature ovarian failure. Although 2 per cent of women in the general population have menopause before the age of 40 years, there have been reports of only two kindreds in which heritability of premature failure is suggested. The present report describes five additional kindreds in which idiopathic premature ovarian failure appears to be genetic. In an Ashkenazi Jewish family, two first cousins developed premature failure at ages 33 and 34 years, respectively, (Fig. 1). Their paternal aunt, grandmother, and great aunt all developed the condition at age 32 years. Both fathers would have to be considered obligate carriers. The two probands (A and B) had normal physical and pelvic ultrasound examinations. Endocrine studies documented hypergonadotropic hypogonadism. No anti-ovarian antibodies were demonstrated. Careful karyotypic examination by Giemsa banding failed to reveal any subtle X-chromosome abnormality, and all karyotypes were 46,XX. In three generations of a Hispanic kindred, ovarian failure occurred at ages 36, 30, and 24 years. The proband, who developed failure at age 24 years, had normal results from physical and ultrasound examinations. Studies showed elevated gonadotropins, normal karyotype, and no anti-ovarian antibodies. This patient had laparoscopic ovarian biopsy, in which no follicles were seen. In an Anglo-Saxon Protestant kindred, the proband developed ovarian failure at age 30 years, close to the age at which her monozygotic twin sister failed. The proband was aware of the family trait and sought advice for her premenarchal daughters. Fig. 1. Ashkenzi Jewish family. Two first counsins (A and B) developed premature ovrain failure at ages 33 and 34, respectively. Their paternal aunt, grandmother, and great aunt all had menopause at age 32. By our reasoning, the two fathers would have considered obligate carriers of the trait. The proband in an Italian kindred, a 27-year-old primi-para who had been exposed to diethylstilbestrol in utero, sought counseling about future pregnancies. Her mother had had ovarian failure at age 39 years, and her maternal grandmother had developed it at age 31 years. Physical and pelvic ultrasound examinations of mother and daughter showed normal results, and their karyotypes were 46.XX. In another Hispanic pedigree, the proband had normal periods until age 36 years, when they became irregular. Menses ceased at age 37 years. Two of her sisters became menopausal at ages 25 and 33 years, respectively, and their mother was menopausal at age 28 years. Physical and ultrasound examinations and karyotypic analysis were negative. There were no anti-ovarian antibodies.