Sex differences in blood pressure are evident in experimental models and human subjects, yet the mechanisms underlying this disparity remain equivocal. The current study sought to define the extent of male-female differences in the circulating and tissue renin-angiotensin aldosterone systems (RAAS) of the congenic mRen2.Lewis and the control Lewis rats. Male congenics exhibited higher systolic blood pressure than females [200 +/- 4 vs. 146 +/- 7 mmHg, p =0.01] or Lewis males and females [113 +/- 2 vs. 112 +/- 2 mmHg, p >0.05]. Plasma Ang II levels were 2-fold higher in male congenics [47 +/- 3 vs. 19 +/- 3 pM, p =0.01] and 5-fold higher than male or female Lewis [6 +/- 1 vs. 6 +/- 1 pM]. Ang I levels were also highest in the males; however, plasma Ang-(1-7) was higher in the female congenics. Male congenics exhibited greater circulating renin and ACE activities than their female littermates. Renal cortical and medullary Ang II levels were also higher in the male congenics versus all other groups; Ang I was lower in the males. Cortical ACE2 activity was higher in male congenics, yet neprilysin activity and protein were greater in the females and ACE activity was similar for all groups. These data reveal that sex differences in both the circulating and renal RAAS are apparent primarily in the hypertensive group. The enhanced activity of the RAAS in male congenics may contribute to the higher pressure and tissue injury evident in the strain. Key words: Ang II, Ang-(1-7), estrogen, ACE2, neprilysin.