Fluid and electrolyte homeostasis in preterm newborns is compromised due to immature renal function. Antenatal glucocorticoid treatment 48 h prior to preterm delivery has been shown to augment preterm newborn kidney adaptive responses. To assess kidney responses to short-term antenatal glucocorticoid exposure, renal responses to intravascular volume expansion were compared in preterm (123 d gestation; term=150 d) newborn lambs delivered 15 h after receiving direct fetal (FET; n=8) or maternal (MAT; n=9) betamethasone (0.5 mg/kg) treatment or saline (SAL; n=9). Lambs were cesarean delivered, treated with Survanta(r) and ventilated. After 2 h, urine flow (Uflow), sodium excretion (UNaV) and osmolar clearance (Cosm) values were not different among the SAL and betamethasone treated groups. Volume expansion(saline =2.5% of body weight over 10 minutes) increased mean±SEM(p<0.05) values for Uflow (0.23±0.04 to 0.58±0.09 ml/min/kg), UNaV (29.7±5.8 to 76.2±12.3 μEq/min/kg) and Cosm (12.2±1.2 to 24.3±1.6 ml/100 ml GFR) in the FET group. Comparable increases in urine values were observed in the MAT group while SAL values did not change. Conclusion: Short-term (15 h) antenatal betamethasone exposure is sufficient to significantly augment preterm newborn kidney adaptive responses to acute volume expansion by 2 hr following delivery.