In young adult spontaneously hypertensive rats (SHR), mean arterial pressure (MAP) is higher in males than females and inhibition of the renin-angiotensin system (RAS) removes the sex difference. After cessation of estrous cycling in the females, MAP becomes similar between the sexes. The purpose of this study was to determine the role of the RAS in maintenance of the hypertension in aging male and female SHR. Males and females, 16 mos, had similar MAP (183±5 vs. 193±8 mmHg), and chronic losartan (40 mg/kg/d po, 3 weeks) reduced MAP by 52% (to 90±8 mm Hg, p<0.05 compared to control) in males but by 37% (to 123±11 mm Hg, p < 0.05 compared to control) in females (p<0.05 females compared with males). AT1 receptor blockade was similar since MAP responses to acute doses of Ang II (62.5-250 ng/kg) were blocked to a similar extent in losartan-treated males and females. F2-isoprostane excretion was reduced more with losartan in males than females. There were no sex differences in plasma renin activity, plasma angiotensinogen or angiotensin II (Ang II), or in renal expression of AT1 receptors, angiotensin converting enzyme (ACE) or renin. However, renal angiotensinogen mRNA and protein expression was higher in old males than females, whereas renal Ang II level was higher in old females than males. The data show that in aging SHR when blood pressures are similar, there remains a sexual dimorphism in the response to AT1 receptor antagonism and that the differences may involve sex differences in mechanisms responsible for oxidative stress with aging.