The renin-angiotensin system (RAS) is a candidate mechanism linking altered nutrition in early life to cardiovascular dysfunction. Previously we have shown that in 1 year-old sheep the postnatal blood pressure response to frusemide is modified by nutrient restriction from conception to day 30 of gestation (Cleal et al., 2003). In this study we investigated the effects of postconceptional and postnatal nutrient restriction on RAS function in adult sheep at 2.5 years of age. Welsh Mountain ewes (UK Animals Scientific Procedures Act 1986) received 100% (group C, n=37) or 50% of global nutrient requirements (group U, n=40) from conception to day 30 of gestation, and 100% thereafter. Offspring were then fed either ad libitum (CC, n=20 and UC, n=19) or at a level that reduced body weight to 85% of individual target weight (predicted from 0-12 week growth trajectory) from 12-25 weeks postnatal age and ad libitum thereafter (CU, n=17 and UU, n=21). Each group contained approximately equal numbers of males and females. At ~2.5 years of age catheters were inserted into the carotid artery and jugular vein under general anaesthesia (3% halothane/O₂). RAS function was assessed using an angiotensin II bolus (0.05μg/kg; i.v.) and a frusemide challenge (5mg/kg; i.v.) and heart rate (HR), mean arterial blood pressure (MAP), diastolic (DBP) and systolic blood pressure (SBP) were monitored. Data (mean±S.E.M.) were expressed as area under the curve (AUC) and maximum response, and were analysed by ANOVA. In males, but not females, postconceptional nutrient-restricted offspring (UC and UU) had a smaller MAP, DBP and SBP response to angiotensin II at 2.5 years of age (P<0.05) compared with controls (CC and CU). In addition, UC males had a greater decrease in HR in response to angiotensin II (P<0.05) compared with CC, which was not seen if they received a subsequent postnatal nutrient restriction (UU). Moreover, male offspring that received a postconceptional nutrient restriction (UC) had a greater maximum HR decrease and HR AUC in response to frusemide (P<0.05) compared with CC, but not if they also received a postnatal nutrient restriction (UU). This study suggests that RAS mechanisms of cardiovascular control in adulthood are influenced by diet in early life. The sex-specific interaction between postconceptional and postnatal nutrition on heart rate responses to RAS challenge may indicate altered baroreflex mechanisms and could have consequences for renal/cardiovascular function in later life.