Birth is characterized by a surge in sympathetic outflow, heart rate (HR), mean arterial blood pressure (MABP) and circulating catecholamines. The paraventricular nucleus (PVN) of the hypothalamus is an important central regulatory site of sympathetic activity, but its role in the regulation of sympathoexcitation at birth is unknown. To test the hypothesis that the PVN regulates sympathetic activity at birth, experiments were performed in chronically instrumented near term (137-142 d gestation, term 145 d) sheep before and after delivery by cesarean section. Stereotaxically guided electrolytic lesioning of the PVN (n=6) or sham lesioning (n=6) was performed 48 hours prior to study. At 30 min after birth, renal sympathetic nerve activity (RSNA) increased 128 ±26% above fetal values in the sham lesioned animals (p<0.05). In contrast, at a similar time point, RSNA decreased to 52 ±12% of the fetal value in the PVN lesioned animals. Lesioning of the PVN did not affect the usual postnatal increases in MABP and epinephrine levels although heart rate failed to rise above fetal values. Angiotensin II but not arginine vasopressin or norepinephrine levels increased in PVN lesioned animals after birth whereas all three hormones increased (p < 0.05) in sham animals. Fetal and newborn heart rate baroreflex responses were similar in both groups. However, the usual postnatal attenuation of baroreflex mediated inhibition of RSNA was blunted in the PVN lesioned group. The results of this study demonstrate that ablation of the PVN abolishes sympathoexcitation with birth at near-term gestation. The PVN may play a critical role in physiologic adaptation at birth.