The present study investigated the role of delta-opioid receptors (ORs) in estrogen facilitation of female rat reproductive behavior (lordosis). Infusion of 2 microg of the selective delta-OR agonist [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE), into the third ventricle facilitated lordosis behavior in ovariectomized (OVX) rats injected with estrogen (E) 48 and 24 h before behavioral testing. Pretreatment with the selective delta-OR antagonist naltrindole (NTDL) blocked DPDPE effects on lordosis behavior. Ventricular infusion of NTDL (40 microg) also suppressed lordosis behavior in fully receptive OVX rats primed with both E and progesterone (P). In addition, NTDL blocked lordosis behavior when infused into the ventromedial nucleus of the hypothalamus (VMH) but not into the medial preoptic area (mPOA). Site-specific infusion of DPDPE into the VMH had dose-dependent, dual effects on lordosis behavior. While a very low dose of DPDPE (0.01 microg) facilitated lordosis behavior, a higher dose (1.0 microg) inhibited receptivity in OVX rats primed with E and a low dose (50 microg) of P. We used 3H-DPDPE to measure the density of delta-ORs in OVX rats treated with vehicle or with E by receptor autoradiography. E treatment did not have any effect on the density of DPDPE binding sites in the VMH, mPOA, medial amygdala, or caudate putamen. The behavioral effects of the ligands used in this study suggest that activation of delta-OR in the VMH by endogenous opioids facilitates estrogen-dependent lordosis behavior.