AbstractThe susceptibility of chick embryos to the teratogenic action of intraamniotically injected hydrocortisone increases by several orders during the first four days of incubation. An attempt was made to correlate this phenomenon with the appearance of specific intracellular binding proteins for glucocorticoids. The binding of [3H] corticosterone to the soluble cytoplasmic proteins of the chick embryo was investigated on days 1.5, 2, 3, and 4 of incubation using a gel filtration method. No evidence of high affinity binding was found in embryos on day 1.5. High affinity binding of [3H] corticosterone to the cytosol proteins was first observed in embryos on day 2, but the binding capacity was four times lower than that found in embryos on days 3 and 4. A correlation was obtained between the increasing sensitivity of the chick embryo to hydrocortisone and the appearance of the intracellular binding protein for glucocorticoids. The causal relationship between these two phenomena is further supported by the finding that administration of a nonteratogenic dose of cortexolone completely prevents the teratogenic “cleft beak” action of hydrocortisone, presumably on the basis of competition for binding sites to the glucocorticoid receptor. These findings are consistent with the hypothesis that the teratogenic action of glucocorticoids is mediated by specific cytoplasmic receptors in the chick emb