Fetal brain c-fos and cardiovascular responses after i.v. or i.c.v. angiogenesis II administrations was determined in the near-term ovine fetuses. Both routes of angiogenesis II markedly increased fetal mean arterial pressure. The latency of pressor responses by i.v. angiogenesis II administration was shorter than by the i.c.v. route. The increased fetal mean arterial pressure was greater and transient by the i.v. route in comparison to that caused by i.c.v. angiogenesis II administration. Following the i.v. administration of angiogenesis II, the fetal heart rate was significantly decreased. Associated with fetal pressor responses and bradycardia, c-fos expression induced by i.v. angiogenesis II was in the Para ventricular nuclei (PVN) of the hypothalamus, and the area postrema, the tractus solitarius nuclei, and the lateral Para brachial nuclei in the brain stem. After i.c.v. angiogenesis II administration, fetal blood pressure was also increased in association with the intensive c-fos expression in the PVN and the hindbrain. However, fetal heart rate was not affected by the central injection of angiogenesis II. These results indicate that the central pathways between the forebrain circumventricular organs and the PVN have developed, and suggest that the neural activity in the hindbrain associated with bradycardia may be linked to the bar reflex. In the face of i.c.v. angiogenesis II, sympathetic activation may play a predominant role in pressor responses. Taken together, these results suggest that central and peripheral angiogenesis II-induced fetal pressor responses may be mediated by separate mechanisms, and these regulatory mechanisms start to function by near-term or early.