Morphological and behavioral responses to estradiol-17/3 (Ez-ll/3) and estradiol-17a (E2-17«) were examined in a series of three experiments. The Ea-17/3 augmented uterine growth in hamsters to a greater extent than did E2-17a. Lordosis in ovariectomized adults was elicited by treatment with Eg-17/3 but not with E2-17« (each tested in combination with progesterone). When administered neonatally, only E2-17/3 disrupted estrous cyclicity in the intact female and induced the ability to mount in ovariectomized, androgen-treated adults. These results suggest the existence of a stereospecific response to estrogenic stimulation in neural tissue comparable with that occurring in the uterus.The specific molecular requirements of estrogen-sensitive sex ducts of female mammals have been investigated in some detail. Studies of rodent uteri have demonstrated the existence of a cellular receptor for estadiol-17/3 (E 2 -17/3) that interacts only weakly with nonestrogenic steroids. Although less effective than E 2 -17^, other estrogens compete with radiolabeled E2-17/8 to varying degrees for binding to the E2-17/3 receptor (Gorski, Toft, Shyamala, Smith, & Notides, 1968). The estrogen estradiol-17a (E2-17a) has been particularly useful in the study of estrogen binding in the uterus. Although differing from E2-17/3 only in the position of the hydroxyl group at carbon 17, Ea-17o! competes poorly for binding to the E 2 -17 (3 receptor (Noteboom & Gorski, 1965;Puca & Bresciani, 1968;Terenius, 1965), a result that indicates the high degree of stereospecificity of the estrogen-uterus interaction.The stereospecificity of estrogenic stimulation of neurobehavioral processes has