Data are presented on the sex-specific frequency and the sex ratios of anencephaly and spina bifida from 1945 through 1971. Dramatic changes in the overall rate of these malformations occurred during that period. The purpose of this study was to evaluate the concept of sex-specific thresholds for an unidentified environmental teratogen, a concept which had recently been proposed. The observed epidemiologic relationship between the frequencies and the sex ratios of these malformations is too complex to reconcile with the action of a single teratogen. On hypothetical grounds, a deficiency of human chorionic gonadotrophin (HCG) could explain the sex ratio pattern. These malformations might be caused by yet unidentified factors which produce a deficiency in HCG function. These factors could be placental teratogens, or they could be some other type of environmental agent which is capable of producing a long-term effect on maternal endocrine function.