Hypothyroidism patients have increased cardiovascular risk, although the mechanism is not defined. Endothelial dysfunction may initiate atherosclerosis, is present in patients with hypothyroidism, and therefore may link hypothyroidism and vascular disease. We are unaware of studies examining the effect of thyroid replacement therapy on endothelial function in hypothyroid patients. The present study examined the effect of treatment of hypothyroidism on brachial artery reactivity. Consequently, we measured endothelium-dependent (EDV) and endothelium-independent (EIV) vasodilation using brachial artery ultrasonography in 8 hypothyroid patients (5 men, mean age 48.9 +/- 5.5 years; mean thyrotropin [TSH] 49.0 +/- 37.0 mIU/L) before and after thyroxine treatment. Thyroxine treatment reduced average TSH to 2.9 +/- 0.5 mIU/L and improved EDV (8.0% +/- 4.4% v 3.4% +/- 2.5%, P <.05), whereas EIV was unchanged (20.3% +/- 6.1% v 19.2% +/- 9.4%, P = not significant [NS]). Thyroxine treatment did not alter serum lipids. Thyroid replacement therapy improves endothelium-dependent vascular reactivity in patients with hypothyroidism irrespective of lipid changes.