Ang (1-7) contributes to the blood pressure (BP) lowering effect of angiotensin receptor blockers (ARBs) in male experimental animals. Females have greater Ang (1-7) concentrations than males; however, the contribution of Ang (1-7) to ARB-mediated decreases in BP in females is unknown. The current study tested the hypothesis that female SHR have a larger Ang (1-7) contribution to the BP lowering effects of the ARB candesartan than male SHR. 12 wk old male and female SHR were randomized to receive: candesartan (0.5 mg/kg/day; 7 days); candesartan plus Ang II (200 ng/kg/min; 7 days); the Ang (1-7) antagonist A-779 (48 µg/kg/hr) plus candesartan and Ang II. Candesartan decreased basal BP in males and females (Baseline vs Candesartan: 142±2 vs. 122±3 and 129±1 vs. 115±1 mm Hg, respectively; p<0.05); however, the decrease was greater in males. Ang II increased BP in males in the presence of candesartan (149±2 mm Hg; p<0.05); candesartan blocked Ang II-induced increases in BP in females (116±1 mm Hg). Pre-treatment with A-779 abolished candesartan-mediated decreases in BP in females, but not males. A-779 also exacerbated Ang II-induced proteinuria (26±6 vs. 77±11 µg/kg/day; respectively; p<0.05) and nephrinuria (20±5 vs. 202±58 µg/kg/day; respectively; p<0.05) in candesartan-treated female SHR, with no effect in males. In conclusion, females are more sensitive to the BP lowering effect of ARBs during Ang II infusion, while males are more sensitive under basal conditions. In addition, Ang (1-7) has a greater contribution to ARB-mediated decreases in BP, protein and nephrin excretion in females relative to males.