An experiment was conducted in pigs to determine the source of fetal cortisol at 50 (n = 5) or 100 days (n = 4) of gestation (term = 114 days). Equilibrium concentrations of tritiated cortisol were achieved, and all hormonal measures were made at 110, 130, 140, and 150 min in anesthetized pigs. Maternal plasma cortisol did not differ (p = 0.48) between 50 (70.2 +/- 7.4 ng/ml; mean +/- SEM) and 100 days (62.4 +/- 5.8 ng/ml). Conversely, fetal cortisol increased (p = 0.048) between 50 (8.5 +/- 2.5 ng/ml) and 100 days (24.2 +/- 4.2 ng/ml), and, at each gestational age, values were lower (p = 0.001) than those in maternal plasma. Plasma cortisone (15.1 +/- 2.3 ng/ml) did not change with gestational age (p = 0.42) in either compartment (maternal or fetal), nor did it differ between compartments (p = 0.08). Maternal cortisol accounted for 22.8 +/- 2.0% of fetal cortisol at 50 days of gestation, and this contribution decreased (p < 0.001) to 5.87 +/- 0.8% at 100 days. At both ages, maternal cortisol accounted for almost 50% of fetal cortisone. Metabolism of maternal cortisol by the entire uterofetoplacental unit was 8.4 +/- 1.7% at 50 days and 7.5 +/- 2.4% at 100 days (p = 0.76). The maternal metabolic clearance rate of cortisol increased 44% (p = 0.003) between 50 and 100 days (1.49 +/- 0.4 vs. 2.15 +/- 0.2 L/min). Hence at these gestational ages, the fetus--presumably the fetal adrenal--is the primary source of fetal plasma cortisol. The major contribution of maternal cortisol to fetal cortisone strongly suggests the presence of porcine placental 11 beta-hydroxysteroid dehydrogenase activity. Further, factors constituting the placental "barrier" that metabolize maternal cortisol to cortisone and other products may be major regulators of porcine fetal plasma cortisol and cortisone.