OBJECTIVE To investigate the effects of postmenopausal hypoestrogenism on the content of autonomic vasoconstrictor (neuropeptide Y) and vasodilator neuropeptides (vasoactive intestinal peptide and substance P) at the arterial level. METHODS Prospective, clinical study. METHODS Department of Gynecology and Obstetrics and Pathophysiology of Human Reproduction, University of Naples "Federico II," Naples, Italy. METHODS Twenty premenopausal women and 20 postmenopausal women, matched for age and parity. METHODS All patients underwent abdominal hysterectomy with bilateral oophorectomy for benign conditions. During surgery, a sample of uterine artery was obtained. The presence of E2, estrogen receptor alpha (ER alpha), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), and S100 (a generic neuronal marker) was evaluated by means of immunohistochemistry and Western-blot analysis. METHODS Mean arterial content of E2, ER alpha, VIP, NPY, and SP. RESULTS Both immunohistochemical and Western-blot analysis showed that after menopause, the reduction in E2 and ER alpha in the uterine artery wall is associated with a decrease in vasodilator neuropeptides and an increase in vasoconstrictor NPY. A similar immunopositivity for S100 was observed in pre- and postmenopausal samples, which demonstrated similar total neuronal fiber contents. CONCLUSIONS Postmenopausal hypoestrogenism seems to increase arterial vascular tone through a reduction of vasodilator neuropeptides and an increase in vasoconstrictor peptides in the arterial-wall termination of the autonomous system. These changes in neuropeptide content in the arterial walls might represent a new mechanism underlying the negative effects of menopause on the cardiovascular system.