Sex hormone binding globulin (SHBG) is found in the brain and acts directly on plasma membrane-associated receptors in the prostate gland. Infusing SHBG into the medial preoptic area or medial basal hypothalamus of female rats increases their female sexual receptivity. SHBG, SHBG plus estradiol (SHBG-E), and SHBG-E plus oxytocin all significantly increased female sexual receptivity over vehicle or estradiol plus oxytocin infused controls, as measured by lordosis quotients and receptivity scores, at 40, and 90 min after their infusions into the medial preoptic area. When infused into the medial basal hypothalamus, SHBG-E plus oxytocin resulted in significantly increased sexual receptivity 20 and 40 min after infusion when compared to its estradiol plus oxytocin control group. SHBG produced in the brain may be released endogenously to have immediate effects on reproductive physiology and behavior.