Maternal and fetal progesterone (P₄) metabolism and placental transfer were examined in vivo. Via a femoral vein, 3.2 μCi [¹⁴C]P₄ were infused at a constant rate for 2 h into five rhesus macaques on days 131–137 of gestation. Simultaneously, 12 μCi [³H]P₄ were infused into the fetuses via a placental bridging vein. Measurement of steady state concentrations of [¹⁴C]- and [³H]P₄ in the maternal and fetal circulations permitted calculation of the MCRs, production rates (PRs), and transfer rates (Vs) of P₄. The maternal MCR (533 liters/day) was higher than the fetal MCR (93 liters/day), whereas the maternal PR did not differ significantly from the fetal PR (2.3 and 1.0 mg/day, respectively). Placental transfer of P₄ from the fetal to maternal circulation (V_FM) was greater than that from the maternal to fetal circulation (V_MF). Values were 0.23 and 0.07 mg/day, respectively. The utilization of circulating P₄ as a substrate for fetal cortisol (F) production was examined in three additional monkeys for whom the amount of isotopically labeled P₄ infusate was increased 5-fold. By determining the ratio of specific activities of [³H]F and [³H]P₄ in the fetal circulation, we found the maximum contribution of circulating fetal P₄ as a precursor of fetal F to be less than 1%. Our results indicate that: 1) higher fetal than maternal plasma P₄ concentrations (11.3 and 4.3 ng/ml, respectively) are most likely the result of 5-fold lower fetal MCR, since the PRs are similar in the fetal and maternal compartments, and the V_FM is greater than the V_MF; and 2) fetal F production using circulating P₄ as a substrate is minimal. (Endocrinology117: 1253–1258, 1985)