In the fetus, arginine vasopressin (AVP) has been considered a "stress" hormone with primarily cardiovascular effects. In adult animals, AVP also has substantial endocrine effects, e.g., acting as a corticotropin-releasing factor, an effect not clearly demonstrated in the fetus. Therefore we examined this action of AVP in fetal sheep [135 +/- 1 (SE) days gestation] during a 30-min vasopressin infusion (12 mU/min) while monitoring mean arterial pressure (MAP) and heart rate (HR). Blood samples were obtained before, 15 and 30 min during, and 30 and/or 60 min after the infusion. During vasopressin infusion (n = 11), MAP increased (P less than 0.01), whereas HR fell (P less than 0.01). Plasma AVP increased from 2.32 +/- 0.22 to 84 +/- 6.8 and 89 +/- 10 microU/ml (P less than 0.001), whereas adrenocorticotropin (ACTH) rose from 18.0 +/- 2.4 to 27.7 +/- 3.7 and 43.4 +/- 8.0 pg/ml (P less than 0.05) and cortisol from 1.81 +/- 0.36 to 3.48 +/- 0.56 and 3.97 +/- 0.57 micrograms/dl (P less than 0.005) at 15 and 30 min, respectively. Although neither basal nor AVP-induced ACTH increases changed over the period of gestation studied, base-line cortisol concentrations and the absolute rise in ACTH-stimulated cortisol release increased as gestation progressed, demonstrating increased adrenal sensitivity to ACTH. As in adults, AVP stimulates fetal pituitary secretion of ACTH, providing evidence for another role for AVP in fetal adaptation.