The in vivo conversion of progesterone (Prog) to deoxycorticosterone (DOC) was determined in the circulation of men and women. Labeled Prog was given by constant infusion under steady state conditions, and plasma Prog and DOC were isolated by column, paper, and high pressure liquid chromatographies. Blood production rates (PR) were calculated from the product of the morning plasma concentrations measured by RIA and the MCR. The DOC MCR was determined using data from our previous study. In men, the Prog and DOC levels were 9.8 ± 2.3 (±SE) and 7.8 ± 0.4 ng/dl, respectively. The Prog, MCR averaging the 105 and 120 min samples, was 1968 ± 132 liters/ day, and the PR was 194 ± 46 /xg. The conversion ratio (CR) was 1.3 ± 0.2%, which, taken together with plasma Prog and DOC levels, indicates that less than 2% of plasma DOC was from Prog in blood. Similar data were found in women in the follicular phase. Plasma levels of Prog and DOC were 8.3 ± 1.0 and 6.4 ± 0.6 ng/dl, respectively. The MCR was 1955 liters/day, the Prog PR was 162 ± 13 jug/day, and the DOC PR was 84 ± 8 /ig/day. Since the CR was 1.4%, again, less than 2% of DOC was from circulating Prog. However, in the midluteal phase, plasma Prog rose to 1073 ± 101 ng/dl, and DOC increased to 15.6 ±1.1 ng/dl (P < 0.001). The Prog MCR and PR were 2246 ± 302 liters/day and 24.6 ± 2.3 mg/day, respectively, with a DOC PR increasing to 204 ± 14 jitg. Despite the finding that the CR remained at 1.2 ± 0.2%, the calculations indicate that 83% of the DOC in the luteal phase is from Prog.These studies indicate that Prog can be 21-hydroxylated to DOC by peripheral tissue, but the conversion seems to be unaffected by sex or the precursor level. In men and in women in the follicular phase, DOC in plasma is from direct adrenal secretion. However, in the normal luteal phase, most plasma DOC (more than 75%) is derived from Prog secreted by the corpus luteum. (J Clin Endocrinol Metab 56: 93, 1983)