Activation of the sympathoadrenal system is vital in regulating the physiological adjustments at birth. We have shown in near-term fetal sheep that renal sympathetic nerve activity (RSNA) increases rapidly at birth (250%) and parallels the rise in heart rate and arterial pressure (Am J Physiol 267:H1824, 1994); the sympathetic response in preterm fetal sheep at birth is not known. To test the hypothesis that the increase in RSNA at birth is impaired in immature lambs, experiments were performed in chronically instrumented preterm fetal sheep (118-127 d gestation, term 145 d) studied before birth and following delivery by cesarean section. One hour after delivery (pH 7.22 ± 0.05, PO2 92 ± 34 mmHg) mean arterial blood pressure (MABP, 52 ± 4 mmHg) but not heart rate (HR, 179 ± 21 bpm) was significantly increased (p<0.05) above fetal values (46± 3 mmHg and 195 ± 10 bpm, respectively). However, in contrast to term sheep, RSNA actually decreased following birth, achieving only 39± 17% of fetal RSNA (p<0.05) (n=5). Since cardiovascular responses at birth are improved by the use of antenatal corticosteroids, we also tested the hypothesis that corticosteroid administration would evoke a more mature sympathetic response at birth. After maternal administration of dexamethasone 5 mg/d × 48 h, 4 of 6 fetuses showed an increase in RSNA above fetal value (145±60% of fetal RSNA, n=6), compared with 0/5 non-steroid treated animals. These results suggest that sympathoexcitation is impaired following premature delivery, which may contribute to the depressed cardiovascular and metabolic responses at birth in preterm infants. Furthermore, antenatal corticosteroid treatment appears to have a maturational effect on the sympathetic response at birth. This may be one mechanism by which maternal steroid administration improves cardiovascular homeostasis after birth and lessens the incidence of complications associated with disordered hemodynamic regulation.