Estrogen replacement therapy significantly reduces the risk of cardiovascular disease in postmenopausal women. Previous studies indicate that estradiol (E₂) decreases angiotensin II (AT) receptor density in the adrenal and pituitary in NaCl-loaded rats. We used an in vivo model that eliminates the potentially confounding influence of ACTH to determine whether the E₂-induced decrease in adrenal AT receptor expression affects aldosterone responses to angiotensin II (Ang II). Female rats were ovariectomized, treated with oil (OVX) or E₂ (OVX+E₂; 10 μg, sc) for 14 days, and fed a NaCl-deficient diet for the last 7 days to maximize adrenal AT receptor expression and responsiveness. On days 12–14 rats were treated with dexamethasone (DEX; 25 μg, ip, every 12 h) to suppress plasma ACTH. On day 14 aldosterone secretion was measured after a 30-min infusion of Ang II (330 ng/min). Ang II infusion increased the peak plasma aldosterone levels to a lesser degree in the OVX+E₂ than in the OVX rats (OVX, 1870 ± 290 pg/ml; OVX+E₂, 1010 ± 86 pg/ml; P < 0.05). Ang II-induced ACTH and aldosterone secretion was also studied in rats that were not treated with DEX. In the absence of DEX, the peak plasma aldosterone response was also significantly decreased (OVX, 5360 ± 1200 pg/ml; OVX+E₂, 2960 ± 570 pg/ml; P < 0.05). However, E₂ also reduced the plasma ACTH response to Ang II (P < 0.05; OVX, 220 ± 29 pg/ml; OVX+E₂, 160 ± 20 pg/ml), suggesting that reduced pituitary ACTH responsiveness to Ang II contributes to the effect of E₂ on Ang II-induced aldosterone secretion. Adrenal AT₁ binding studies confirmed that E₂ significantly reduces adrenal AT₁ receptor expression in both the presence and absence of DEX in NaCl-deprived rats. These results indicate that E₂-induced decreases in pituitary and adrenal AT₁ receptor expression are associated with attenuated pituitary ACTH and adrenal aldosterone responses to Ang II and suggest that estrogen replacement therapy may modulate Ang II-stimulated aldosterone secretion as part of its well known cardioprotective actions.