In the present investigation, we determined the levels of deoxycorticosterone sulfate in mixed umbilical cord plasma of anencephalic abortuses and newborn infants. The anencephalic fetus is an interesting model with respect to the production of deoxycorticosterone and deoxycorticosterone sulfate on several accounts. There is profound adrenal atrophy in most such fesuses, and, in consequence, there also is relatively profound hypoestrogenism. This is an important consideration in the formation of deoxycorticosterone and deoxycorticosterone sulfate since it is known that estrogen acts to stimulate extra-adrenal steroid 21-hydroxylase and 21-hydroxysteroid sulfotransferase activities. The plasma levels of deoxycorticosterone sulfate in 22 anencephalic abortuses and newborn infants delivered between 21.5 and 45.5 weeks of gestation ranged from 1.8 to 30.3 ng/ml. The concentrations of deoxycorticosterone sulfate in umbilical cord plasma of anencephalic fetuses and newborn infants were not related to gestational age or method of delivery and, at term, were less than 13% of those in umbilical cord plasma of normal newborn infants. These data can be interpreted to indicate (1) that deoxycorticosterone sulfate normally is secreted directly by the fetal adrenal or (2) that placental estrogen normally derived largely from fetal adrenal dehydroisoandrosterone sulfate is essential for the maintenance of plasma deoxycorticosterone sulfate levels in the fetus by stimulating extra-adrenal deoxycorticosterone sulfate production from plasma progesterone, or both.