The metabolic interrelationship between cortisol (F) and cortisone (E) was studied in four long term catheterized rhesus monkey fetuses in utero during the last third of gestation. The MCR of E (50.8 +/- 5.4 liters/day) was greater than that of F (22.4 +/- 2.1, P less than 0.005) as was the plasma concentration (187.9 +/- 5.0 vs 86.1 +/- 2.5 ng/ml, P less than 0.001). The production rate of E (9.6 +/- 1.4 mg/day) was several-fold greater than for F (1.9 +/- 0.2, P less than 0.005). Of all fetal F, 79.5 +/- 7.0% was metabolized to E, and 43.4 +/- 3.9% originated from E within the fetal circulation. A significant mass of F was infused in these experiments because of the low specific activity of [14C]F. Nevertheless, the fetus was able to maintain F concentrations in the normal range. The MCR of F was similar to that which we previously found using trace amounts of [3H]F. This indicates that the fetus regulates the amount of F in the fetal compartment, probably by decreasing fetal; adrenal secretion rate. We conclude that F in the primate fetus is extensively oxidized to E. We conclude also that E is produced and metabolized much more extensively than is F. Reduction of E back to F could be an important source of fetal F, and increasing activity of this pathway, if present, could contribute to the increase in fetal F levels observed in late gestation in the primate.