The effect of intravenous angiotensin II (ANG II) on fetal brain c-fos expression and arginine vasopressin (AVP) release was studied in the nearterm ovine fetus. The fetuses with chronically implanted catheters received an intravenous infusion of ANG II or saline. Fetal plasma AVP concentrations were significantly increased after the peripheral administration of ANG II, with peak levels (3 fold) at 30 minutes following the intravenous infusion. There was no change in fetal plasma osmolality, sodium, and hematocrit levels between the control and the experimental groups, or between the periods before and after the infusion of ANG II. Intravenous ANG II administration induced FOS-immunoreactivity (FOS-ir) in the circumventricular organs and the median preoptic nucleus (MnPO) of the fetal brain. FOS-ir was also demonstrated in the fetal supraoptic nuclei (SON). Double labeling demonstrated that the AVP-containing neurons in the SON were expressing c-fos in response to intravenous ANG II. These results indicate that the peripheral ANG II in the fetus may play a significant role in stimulating the central hypothalamic-neurohypophysial system during late gestation. It supports the hypothesis that circulating ANG II may act at the fetal AVP neurons in the hypothalamus in body fluid balance via the circumventricular organs which are situated outside the blood-brain barrier, and the central neural pathway between these two brain structures has been relatively established in utero at least at nearterm.