The present study was designed to determine whether the baboon fetal pituitary at midgestation was responsive in utero to a bolus injection of CRH. On day 100 of gestation (term = day 184), baboons were anesthetized with halothane/nitrous oxide, the fetus was exteriorized, and a cannula was inserted into a fetal carotid artery. Five minutes later (experimental time zero), a fetal carotid blood sample was obtained, and saline (0.5 ml) with (n = 6) or without (n = 3) ovine CRH (100 ng estimated to equal 500 ng/kg BW) was then infused via the fetal carotid over a 3-min period. Fetal blood samples were taken 5, 15, 30, 45, and 60 min post-CRH/saline treatment and assayed for ACTH. Mean (+/- SE) pretreatment fetal plasma ACTH concentrations were similar in animals that subsequently received saline (26 +/- 3 pg/ml) or CRH (29 +/- 6 pg/ml). Fetal plasma ACTH remained constant after the infusion of saline. In contrast, CRH increased (P less than 0.05) fetal plasma ACTH within 5 min in six of six baboons to a value (58 +/- 12 pg/ml) that exceeded (P less than 0.05) the zero time value and the respective mean value (27 +/- 5 pg/ml) in saline-treated fetuses. Fetal plasma ACTH concentrations continued to rise in four of six baboons 15 min after CRH injection to a level (68 +/- 15 pg/ml) which exceeded that in saline controls (27 +/- 2 pg/ml). In fetuses treated with CRH, overall mean fetal plasma ACTH concentrations from 0-60 min increased at a rate (1.47 pg/min) greater (P less than 0.05) than that in fetuses injected with saline (0.07 pg/min). In contrast to the effects of intracarotid CRH injection, fetal plasma ACTH was not increased after the infusion of 100 ng CRH into a fetal antecubital vein of three additional animals. Collectively, these findings indicate that intracarotid injection of a bolus of CRH into the baboon fetus rapidly increased fetal plasma ACTH concentrations. Moreover, the site of action of CRH was presumably the fetal pituitary. Therefore, we suggest that the baboon fetal hypothalamic-pituitary axis at midgestation has the capacity to secrete ACTH in response to a challenge of CRH.