Background: Endothelial dysfunction manifested by diminished flow-mediated dilation of brachial artery has been shown to improve after estrogen substitution in women after menopause. However, there is no data whether the route of estrogen substitution modifies this effect. Subjects and methods: Sixweeks after surgically induced menopause 43 healthy women were randomised, to 28 weeks treatment either by orally or transdermally substitued estradiol. At the beginning, 6 weeks after operation and 28 weeks after oral or transdermal estradiol substitution physical examination and anthropometric measurements were performed and serum total, LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C), lipoprotein(a) (Lp(a)), fasting glucose and plasma plasminogen activator inhibitor (PAI-1) antigen and activity, tissue type plasminogen activator (t-PA) antigen and activity, fibrinogen, antithrombin IH(AT III), protein C, D-dimer, thrombin-antithrombin complex, euglobulin clotlysis time, and serum Creactive protein (CRP) and serum amyloid A were determined. The endothelium-dependent and endothelium-independent dilation were calculated using the diameters of the brachial artery measured by high resolution ultrasound at rest, after reactive hyperemia and after sublingual glyceriltrinitrate. (Abstract truncated at 2000 characters).