<lb>Introduction: There is some evidence about the role of estrogen in the nervous system such, as<lb>increasing plasticity in different areas of brain and interference phenomena like reproduction, pain<lb>and memory. Results of some investigation indicate the neuromodulatory effect of estrogen. In this<lb>study, the effect of estradiol benzoate in morphine dependency was investigated. Material and<lb>Methods: Albino mice weighing 25±3 grams, were divided to in to control (sham operation),<lb>ovariectomized, ovariectomized receiving sesame oil and acute and chronically administrered<lb>estradiol benzoate groups. Addiction was induced in all animals by morphine injections 3 times per<lb>day, for four days. On the fourth day, half an hour before induction of withdrawal syndrome<lb>naloxone, stradiol benzoate were acutely injected (0.1 mg/kg, SC) and jumping of animals as a sign<lb>of withdrawal syndrome was assessed. Chronic treatment of estradiol benzoate was co-<lb>administered with morphine on four the day. Results: The results showed that ovarectomy<lb>decreased jumping activity of withdrawal syndrome or intensity of morphine-dependency and<lb>estradiol benzoate treatment partially increased this sign of the withdrawal syndrome although but<lb>it was less than the control groups. Conclusion: The results suggest that the other sex related<lb>factors probably influence the intensity of morphine dependency.