Although antenatal corticosteroids improve outcomes for preterm newborns, negative effects could result if preterm delivery does not occur. We investigated whether betamethasone treatment of preterm fetal sheep would alter cardiovascular, renal, and lung function after delivery at term. Preterm fetal lambs were randomized at 126-128 days' gestation to receive single doses of saline (n = 6) or 0.5 mg/kg betamethasone (n = 7) by ultrasound-guided fetal intramuscular injection. The lambs were delivered by cesarean at term, 20 days after fetal treatment, then ventilated for 4 hours to evaluate lung, cardiovascular, renal, and endocrine newborn adaptive responses, as well as responses to mild hypoxia. Body and organ weights (brain, lung, heart, kidney, adrenal) were similar in the two groups. Values for blood gases and pH, mean arterial pressures, heart rates, glomerular filtration rates, renal osmolar clearance, and plasma cortisol, angiotensin II, epinephrine, and norepinephrine levels were similar between groups for 3 hours after delivery and before hypoxia. A 20-minute period of mild hypoxia resulted in increases in catecholamines, arginine vasopressin, and atrial natruretic factor in both betamethasone-treated and control lambs. However, hypoxia did not alter cardiovascular or lung function in either group. After reversal of hypoxia, measured physiologic parameters did not differ between groups. Kidney Na, K-adenosine triphosphatase activity was significantly higher for the betamethasone-treated lambs. Preterm fetal betamethasone administration does not alter neonatal pulmonary, cardiovascular, renal, or endocrine physiology after term delivery or in response to mild hypoxia.