Spontaneous water intake as well as thirst elicited by ANG II has been shown to be influenced by the stage of the estrous cycle in the female rat. In these experiments, the contribution of each of the ovarian steroid hormones to the regulation of water intake was examined. Ovariectomized female rats were given replacement doses of estrogen, progesterone, or both, and their responsiveness to an intracerebroventricular injection of ANG II was tested. Forty-eight-hour treatment with estradiol benzoate attenuated ANG II-induced thirst by as much as 70% compared with control animals. The effect of estrogen on drinking was dose dependent and could be completely blocked with concurrent administration of the antiestrogen CI-628. In contrast, progesterone, given alone or after estrogen, did not significantly affect ANG II-induced water intake when animals were tested at 4 or 24 h after steroid administration. A central interaction between the peptide hormone ANG II and estrogen, involving a genomic mechanism, may underlie the cyclicity in water intake behavior observed in the rat.