Previous studies in fetal sheep have concluded that (a) the vascular AT1 angiotensin II (Ang II) receptor subtype is present in the external umbilical artery, but not in other systemic blood vessels, and (b) carotid arterial rings contract in vitro in response to Ang II. These contractions are blocked by the AT1 specific receptor antagonist losartan. The aim of the present study was to resolve the apparent contradiction of these earlier conclusions, by examining the distribution of Ang II receptor subtypes in different regions of the ovine fetal cardiovascular system, and to find out at what stage in development AT1 receptors first appear. We measured AT1 and AT2 receptors in hearts, carotid arteries, aortae and umbilical vessels from fetal sheep aged 65-144 days (term ~150 days), and in hearts and aortae from lambs, and adult pregnant and non-pregnant ewes. Both AT1 and AT2 receptors were present in aortae of fetuses > 118 days gestation, and carotid arteries of fetuses > 121 days gestation, while in younger fetuses only AT2 receptors were found. The proportion of carotid artery and aortic AT1 receptors increased with age, while the proportion of AT2 receptors decreased. The internal umbilical artery contained both subtypes, but there was no relationship between receptor density and gestational age. The external umbilical artery had only AT1 receptors. The highest density of Ang II receptors was found in the fetal heart where the AT2 subtype predominated. The density of fetal cardiac Ang II receptors declined with age (r = -0.44, P < 0.02) due to the decrease in the AT2 subtype. The density in late gestation fetal hearts was greater than in lamb or adult hearts (P < 0.001). Our study shows that fetal systemic blood vessels contain AT1 receptors, and we have documented for the first time that the appearance of AT1 receptors is both different in different regions of the fetal cardiovascular system and is developmentally regulated. Together with the in vitro contractile studies, this suggests that Ang II can play an important role in fetal blood pressure regulation via AT1 receptors in the fetal systemic vasculature, as well in the umbilicoplacental vessels. Experimental Physiology (2001) 86.1, 71-82.