In the current investigation we sought to evaluate fetal adrenal dehydroepiandrosterone sulfate (DS) production during normal human pregnancy. We found that the mean umbilical cord plasma concentration of DS was reasonably constant from 18-34 weeks of gestation, ranging from 1131-1517 ng/ml. Thereafter, the cord plasma DS concentration rose steadily to 2463 +/- 665 ng/ml (mean +/- SD) at 39-40 weeks of gestation. Between 20 and 32 weeks of gestation, the estimated fetal plasma DS pool increased from 8 to 146 microgram. At term, the estimated fetal DS plasma pool was in excess of 300 microgram. From 34-40 weeks of gestation, the estimated fetal DS pool size and the fetal plasma DS concentration increased coincidentally with a marked rise in the known rate of fetal adrenal growth. From these findings, we conclude that fetal adrenal DS production increases steadily throughout gestation, and the rate of increase is probably dependent upon the rate of fetal adrenal growth. Furthermore, the rapid increase in maternal estrogen levels near term observed by numerous investigators can be explained in part by an increased availability of the fetal estrogen precursor DS at this time.