To better understand the sources and regulation of circulating inhibin during primate pregnancy, immunoreactive inhibin was measured in sera obtained from the maternal saphenous vein, uterine vein, and the fetus at varying times of baboon pregnancy. In both intact and fetectomized (fetus removed on day 100 of gestation; term = 184 days) animals, maternal serum inhibin concentrations were relatively constant between day 80 (first sampling day) and day 110 of gestation, after which they then steadily increased until days 155-165 (end of sampling). The increase in inhibin concentrations was significantly less in the fetectomized animals than in the intact baboons. Restoration of estrogen levels in the fetectomized animals did not significantly alter the circulating inhibin concentrations. Similarly, administration of the estrogen antagonist MER-25 to intact animals in the last trimester had no effect on maternal serum inhibin concentrations. Inhibin concentrations in uterine venous blood collected on day 100 of gestation were not significantly different from those in the maternal saphenous vein. However, the inhibin concentrations of uterine venous blood collected late in gestation (days 155-165) in either intact or fetectomized animals were significantly higher than the corresponding maternal venous concentrations, suggesting that the uteroplacental tissue becomes a source of circulating inhibin during the third trimester of pregnancy. Consistent with this suggestion was the detection of inhibin alpha-subunit mRNA in the placentae of intact or fetectomized animals obtained late in pregnancy, but its absence at midgestation. Immunoreactive inhibin concentrations were about 16 times higher (6500 +/- 831 mu Leq/mL) in fetal blood than in maternal blood (411 +/- 23 mu Leq/mL) at midgestation. The fetal blood concentrations significantly decreased to about 2800 mu Leq/mL by days 160-165 of gestation, but were still greater than those in the mother (approximately 1000 mu Leq/mL). The umbilical arterial and venous concentrations were the same as the fetal blood concentration of inhibin. The role of the baboon fetal adrenal in inhibin production was studied. Fetal adrenals collected from days 59, 135, and 167 of gestation contained the mRNA for the inhibin alpha-subunit in relatively high abundance. The in utero administration of ACTH for 30 min to five fetuses at midgestation (days 100-110) apparently did not alter the fetal concentration of immunoreactive inhibin. In summary, maternal serum inhibin levels increase during the last trimester of baboon pregnancy. This is suggested to be due to an increasing contribution of placental inhibin secretion, which is regulated not by placental estrogen production but, perhaps, by placental growth.(ABSTRACT TRUNCATED AT 400 WORDS)