Fluid and electrolyte homeostasis in preterm newborns is compromised due to immature renal function. A single antenatal glucocorticoid treatment augments preterm newborn kidney adaptive responses. To assess the effect of multiple betamethasone (BETA) exposures on kidney adaptation (glomerular autoregulation), pregnant ewes were randomized to receive 1 dose of 0.5 mg/kg BETA at 104d gestation (ONE), 3 doses of BETA at 104, 111, and 118 d gestation(MULT) or saline (control; CON). Lambs were delivered at 125 d (Preterm) or 145 d (Term). Two hours following delivery, Preterm mean arterial pressure(MAP), urine flow (Uflow) and glomerular filtration rate (GFR) did not differ among the groups. Phenylephrine infusion (0.4-26μg/kg/min; over 14 min) increased [mean±SEM (p<0.05)] Preterm MAP (41±3 to 53±4mmHg), GFR (0.59±0.12 to 1.59±0.13 ml/min/kg) and Uflow (0.05±0.03 to 0.16±0.04 ml/min/kg) in the MULT group. While MAP also increased in the ONE and CON groups, GFR and Uflow did not change. Term CON, ONE and MULT responses to phenylephrine infusion were similar to the Preterm MULT increases. Conclusions: 1) Kidney immaturity in preterm newborns includes the absence of renal vascular responses to increases in MAP 2) Preterm newborns exposed to repetitive doses of BETA respond to increased MAP mimicing the term newborn response and 3) Renal maturation at term is not affected by early BETA exposure.