Although there is a good correlation between the levels of gonadal steroids and sex differences in reproductive behavior and food intake, the neurochemical mechanisms by which a gonadal steroid may regulate these behaviors remain unknown. An important central nervous site for steroid modulation of food intake and reproduction is the ventromedial nucleus of the hypothalamus (VMH). Recently it has been suggested that some of the activities of the VMH are dependent on the neuroactive peptide cholecystokinin octapeptide (CCK). High levels of CCK in the VMH have been measured by radioimmunoassay, and immunohistochemical analysis has revealed a dense plexus of CCK fibers and terminals which appose and make synaptic contact with VMH neurons. There is, however, a paucity of information concerning the presence of CCK-binding sites in the VMH. This study demonstrates high levels of 125I-CCK8 binding in the VMH of male and female rats. Tissue sampled on the morning of estrus revealed depressed levels of CCK binding, and, while ovariectomy itself did not affect binding, ovariectomy followed by estrogen replacement depressed CCK binding. These results provide evidence for an estrogenic effect on CCK-binding sites that may help elucidate a role of CCK in the VMH.