Rat ovarian epidermal growth factor (EGF) receptors were characterized in total ovarian homogenate obtained from animals at random stages of the estrous cycle. A single class of specific and high-affinity binding sites with an apparent dissociation constant ( K D) of 1.1±0.2 nM and a total site number of 78±4 fmoles/mg protein (652±17 fmoles/100 mg wet tissue) was observed. In 4-day cycling rats, ovarian EGF receptor levels are high (200 fmoles/100 mg ovary) on the morning of estrus as well as in the afternoon of proestrus and are lower by 30, 60 and 55% on the morning of diestrus I, diestrus II and proestrus, respectively. Chronic administration of an LHRH agonist is accompanied by low ovarian EGF receptor levels comparable to those observed on diestrus II. In intact or hypophysectomized female rats pretreated with pregnant mare's serum gonadotropins, administration of ovine follicle-stimulating hormone or human chorionic gonadotropin increases ovarian EGF receptor concentration and content while the administration of ovine prolactin, 17β-estradiol or progesterone has no effect. Treatment with dihydrotestosterone or testosterone slightly reduces ovarian EGF binding in intact but not hypophysectomized animals. The variation of ovarian EGF receptor levels observed during the estrous cycle as well as the modulation of these receptors by the administration of exogenous gonadotropins suggest that EGF could well play a physiological role in the regulation of ovarian functions.