Desoxycorticosterone (DOC) secretion increases during pregnancy. Administration of adrenocorticotropic hormone (ACTH) to women during the third trimester of pregnancy was noted previously to result in marked sodium retention, while aldosterone excretion declined. Since urinary tetrahydrodesoxycorticosterone increased substantially, sodium retention resulting from ACTH was ascribed to enhanced DOC secretion. Surprisingly, the elevated plasma DOC in late pregnancy failed to respond consistently to ACTH. Effects of ACTH upon total plasma concentrations and free indexes of DOC and cortisol were studied in pregnant women in the third trimester. As a result of ACTH, plasma cortisol and the free cortisol index increased strikingly; the plasma free DOC index rose markedly in those subjects in whom the total plasma DOC level was not altered appreciably and was unchanged or even increased slightly in the few subjects in whom the total DOC level decreased. The results support the proposition that the plasma free DOC fraction is increased because of displacement from corticosteroid-binding globulin by the ACTH-induced increment in cortisol. Resultant elevations of free DOC would not be evident from customary measurements of the total DOC concentration but, nonetheless, could contribute to sodium retention and also would be available for hepatic metabolism.