In the present investigation, we evaluated the origin of deoxycorticosterone sulfate (DOC-SO4) and the production rates of DOC and DOC-SO4 in men and women. Previously, we found that there was little or no interconverion of plasma DOC and DOC-SO4; this finding was reconfirmed in the present investigation. After the iv infusion of [3H]DOC-SO4 and [14C]DOC, urine was collected for 5 days, DOC-SO4 was isolated and purified as unconjugated DOC, and tetrahydro-DOC glucuronoside was isolated and purified as the unconjugated metabolite. The production rate of DOC in these subjects (mean +/- SEM, 66 +/- 9.8 micrograms/24 h) was computed from the specific activity of urinary [14C]tetrahydro-DOC (glucuronoside); the production rate of DOC-SO4 in these subjects (92 +/- 15.9 micrograms/24 h) was computed from the specific activity of urinary [3H]DOC-SO4. The production rates are expressed on the basis of the molecular weight of DOC. Since plasma DOC and DOC-SO4 are not interconverted, we conclude that both steroids are secretory products, presumably from the adrenal cortex.