Antenatal glucocorticoid exposure decreases morbidity in premature newborns by improving renal and cardiovascular functions. The optimal dose and route of betamethasone (BETA) administration for these beneficial effects are unknown. Pregnant ewes (127 d gestation; n=39) were randomized to receive maternal(M) or fetal (F) intramuscular doses of BETA (0.2 or 0.5 mg/kg body weight) or saline as controls. Lambs were delivered 24 hr later by cesarean section, treated with surfactant and ventilated. After 3 hr, 0.2 mg/kg M vs. control mean±SEM values for mean arterial pressure (MAP; 64±4 vs. 47±2 mmHg), glomerular filtration rate(GFR; 1.7±0.2 vs. 0.7±0.1 mL·min-1·kg-1), urine flow (Uflow; 0.21±0.05 vs. 0.03±0.01 mL·mi-1·kg-1) and fractional excretion of sodium(FENa; 10.9±2.2 vs. 3.5±0.6%) were elevated. Although the 0.5 mg/kg F and M BETA treatments also increased MAP and GFR comparable to the 0.2 mg/kg M group, UFlow and FENa values were near or below controls. The 0.2 mg/kg F dose had no measurable effects. Conclusions: 1) Preterm newborn renal and cardiovascular responses to fetal or maternal BETA administration are dose dependent, and 2) Cardiovascular responses to maternal BETA-treatment may occur in the absence of improved renal function.