Background Morphologic changes of the vascular endothelium are common in patients with systemic sclerosis and Raynaud's phenomenon. The aim of this study was to evaluate the endothelium-dependent vasodilatation and endothelium-independent vasodilatation and to examine the effects of short-term estrogen administration on vascular responses in these patients. Methods and Results The study included 12 female patients with systemic sclerosis and Raynaud's phenomenon (aged 49 +/- 14 years) and 12 age- and sex-matched healthy control subjects. With the use of high-resolution ultrasound imaging, brachial artery diameter was measured at rest, during reactive hyperemia (endothelium-dependent response), and after administration of sublingual nitroglycerin (endothelium-independent dilatation). Intima-media thickness of the common carotid artery was also measured. Baseline diameter was similar in patients and control subjects; intima-media thickness was significantly higher in patients (0.83 +/- 0.3 vs 0.46 +/- 0.2 mm, P = .002) than in control subjects. Flow-mediated dilatation was reduced in patients (3.6% +/- 7% vs 11.9% +/- 4.6%, P = .003); endothelium-independent dilatation also was reduced in patients with Raynaud's phenomenon (14% +/- 7% vs 23% +/- 6%, P = .003). Vascular responses in 10 patients were examined 15 minutes after administration of conjugated estrogens (25 mg intravenously); there was a significant increase of endothelium-dependent dilatation after estrogen administration (1.7% +/- 4% to 6.3% +/- 4%, P = .01), whereas endothelium-independent dilatation did not change (13.4% +/- 8% to 15.5% +/- 7%, not significant). Conclusions Endothelium-dependent vasodilatation and endothelium-independent vasodilatation are impaired in patients with Raynaud's phenomenon secondary to systemic sclerosis, whereas intima-media thickness is increased. Shortterm estrogen administration can improve endothelial dysfunction in this group of patients.