Fluoride was first associated with fetal malformation shortly after water fluoridation was initiated in the 1940s. Since many chemicals can interact directly with the embryo to cause malformation, the effects of fluoride on embryonic and fetal development were investigated. The effects of sodium fluoride on the development of frog embryos were studied under conditions described by the Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a screening assay for teratogens. The most prominent malformations caused by sodium fluoride are reduction in the head-tail lengths and dysfunction of the neuromuscular system of the tadpoles. The values for LC50, EC50, and minimal concentration to inhibit growth (MCIG) of sodium fluoride met the limits established for a teratogen in frog embryos, showing that sodium fluoride is a direct acting teratogen on developing embryos. Since FETAX has a high degree of success in identifying mammalian teratogens, the observed teratogenic action of sodium fluoride on frog embryos would indicate a strong possibility that sodium fluoride may also act directly on developing mammalian fetuses to cause malformation.