OBJECTIVE Female sex hormones have several important effects on the venous system. We earlier found that hormone replacement has a significant effect on venous distensibility, but effects of menopause and hormone replacement on venous contractility have never been studied. Therefore, and because the changes we found earlier in distensibility were most likely caused by alterations of contractility, we examined the changes in contractility of saphenous vein caused by depletion and replacement of sex hormones in female rats. METHODS Twenty Sprague-Dawley rats were pharmacologically ovariectomized by triptorelin. Ten of these rats received combined sex hormone replacement (HRT) with estradiol propionate and medroxyprogesterone acetate. The rest were given vehicle. Ten animals without ovariectomy served as controls. After 3 months of treatment, segments of the saphenous vein were dissected. Pressure-diameter curves were recorded in relaxed, contracted, and control states. RESULTS Venous diameter, adjusted for body weight, was significantly decreased after pharmacological ovariectomy. HRT increased the diameter. The presence of sex hormones augmented norepinephrine contraction measured at physiological pressures (control: 19.2 +/- 2.3%; pharmacological ovariectomy: 15.2 +/- 1.4%, p < 0.05 and 17.8 +/- 2.2% following HRT). Myogenic (spontaneous) tone of the saphenous vein did not change after ovariectomy, but it was lowered by hormone replacement (control: 8 +/- 1.1%; ovariectomy: 6.9 +/- 2.5%; ovariectomy + HRT: 2.7 +/- 1.1%, p < 0.05). CONCLUSIONS Sex hormone depletion induces significant alterations in contractility of the saphenous vein, which could perturb venous capacitance function and distensibility. This effect has a potential role in the development of hypertension and venous varicosity, and these changes could possibly be prevented by HRT.