The aromatization of androgens to estrogens in the ovary and the roles of estrogens in promoting follicular growth have been described by a number of investigators. Furthermore, specific receptors for estrogens have been defined in granulosa cells as well as other target tissues. In other estrogen-responsive tissues, there is also a progesterone receptor, which mediates estrogen antagonism at the molecular level. We have previously described an ovarian progesterone receptor in an animal model. We now describe a heat-labile ovarian cytoplasmic protein that specifically binds progestins with a very high affinity. The equilibrium dissociation constant for progesterone (Kd) = 4.8 X 10(-9)M and it is present in the ovary in a concentration of 3.3 X 10(-13) moles/mg of protein. Since the characteristics of this protein are compatible with an ovarian progesterone receptor, there is the implication that the ovary is a target organ for progesterone. Thus, progesterone may have a role in the modulation of ovarian physiology.