The metabolism of cortisol (F) and cortisone (E) in the fetal circulation is likely to influence the availability/biological potency of these corticosteroids and hence maturation of fetal organ systems. Therefore, we determined the MCR, production, peripheral interconversion, and placental extraction of F and E in the baboon fetus at midgestation. Radiolabeled F and E were infused into a femoral vein of fetuses (n = 7; 4 female, 3 male) exteriorized on day 100 of gestation (term = day 184). The MCR of F in the fetus (5.6 +/- 0.8 1/day) was lower (P less than 0.01) than that of E (13.1 +/- 2.2 1/day). Placental extraction of F (72.8 +/- 5.3%) and E (87.8 +/- 2.4%) were extensive indicating that the placenta contributes to fetal F/E MCR. Although the serum concentration (micrograms per dl) of F (20 +/- 2) exceeded (P less than 0.01) that of E (12 +/- 1), the calculated production rate (milligrams per day) of F (1.09 +/- 0.12) was not significantly different from that of E (1.55 +/- 0.27). The transfer constant for fetal conversion of F to E (29.0 +/- 6.0%) exceeded (P less than 0.01) that for reduction of E to F (1.8 +/- 0.4%). Therefore, the proportion of total F production derived from circulating E was only 2.2%, whereas the proportion of E derived from circulating F was 26.7%. These findings demonstrate that at midgestation the baboon fetus has minimal capacity for peripheral conversion of biologically inactive E to biologically active F, whereas the reverse conversion (F to E) is substantial.