The degranulatory activity of estradiol was tested on blood eosinophil leukocytes in vivo and in vitro. Treatment of adult ovariectomized rats with 30 micrograms estradiol/100 g body wt. increased the percentage of degranulated eosinophils from 10% to about 70% at 6 or 24 h after treatment, and increased the rate of in vitro eosinophil degranulation of those eosinophils that were non-degranulated at the time of blood sample collection. The addition of estradiol to blood samples from untreated ovariectomized rats (0.05 micrograms/ml) increased the percentage of eosinophils degranulated in vitro at 1 h of incubation from 20% to near 60%. It is suggested that estrogen acts directly on the eosinophils, probably via specific hormone receptors. Considering the hypothesis that eosinophils are involved in the mediation of a group of responses to estrogen in the uterus, it is proposed that the hormone-induced degranulation of these cells may have physiological implications in the regulation of the intensity and duration of the eosinophil-mediated responses. In addition, estrogen-induced eosinophil degranulation may interfere with the action of eosinophils that have migrated to other target organs (lymphoid organs, etc.) under the action of other agents (glucocorticoid hormones, histamine, etc.) or conditions (immune reactions, etc.).