The relationship of plasma concentrations of arginine vasopressin (AVP), ACTH, cortisol, and PRL in the human fetus to mode of delivery and acid-base status has been investigated in 91 term pregnancies consisting of 4 groups based on mode of delivery, type of anesthesia, and use of ephedrine prophylaxis for maternal blood pressure control. Infants delivered vaginally after uncomplicated labors had higher umbilical cord plasma concentrations of AVP, ACTH, and cortisol than infants delivered without labor. Use of ephedrine, an alpha-agonist, during regional anesthesia was associated with elevated plasma AVP and ACTH concentrations compared to those in women receiving general anesthesia. At the time of delivery, 12 infants had acidemia (pH less than 7.20), as judged by pH of umbilical arterial blood. Their plasma AVP, ACTH, and cortisol levels did not differ from those of infants delivered by uncomplicated vaginal delivery, but were greater than those of infants delivered by cesarean section under general anesthesia. Moreover, in infants with acidemia, plasma concentrations of AVP and ACTH were significantly correlated, but PRL levels were unaffected by mode of delivery or acidemia. Elevated umbilical cord plasma concentrations of AVP, ACTH, and cortisol characterize term vaginal deliveries and are associated with intrauterine stress, demonstrating activation of the fetal hypothalamic-pituitary-adrenal axis and suggesting that AVP is important in ACTH release in the human fetus; however, PRL does not appear to be an important stress hormone.