Background-The presence of endothelial dysfunction with increased endothelin-1 plasma concentrations in patients with cardiac syndrome X is still under debate. The aim of the present study was to evaluate the presence of endothelial dysfunction in patients with cardiac syndrome X. Methods and Results-Endothelin-1 levels were evaluated with a sensitive radioimmunoassay with previous purification through reverse phase HPLC in 24 patients (3 men and 21 women, mean age 54+/-7 years) with typical angina, instrumental evidence of ischemia, and normal coronary angiograms both under baseline conditions and after oral glucose load (75 g D-glucose), We also measured plasma nitrite-plus-nitrate levels, a sharp index of endothelial nitric oxide production, and circulating concentrations of the soluble fraction of the endothelial adhesion molecule vascular cell adhesion molecule-1, a well-recognized marker of early endothelial dysfunction, Fourteen healthy subjects (1 man and 13 women, mean age 47+/-15 years) served as controls. There were no significant differences in baseline plasma endothelin-1 concentrations between patients and control subjects (0.55+/-0.34 versus 0.48+/-0.22 pg/mL, P=0.503). Plasma nitrite-plus-nitrate and soluble vascular cell adhesion molecule-1 concentrations were also similar between the 2 groups. After glucose ingestion, circulating endothelin-1 concentrations were significantly higher in patients with cardiac syndrome X than in control subjects (P<0.03 at 60, 90, and 120 minutes). Conclusions-Our findings show that no basal endothelial damage is present in patients with cardiac syndrome X. Nevertheless, increased responsiveness of endothelin-1 to glucose loading suggests that patients with cardiac syndrome X present an increased susceptibility to releasing endothelin-1 under stressful circumstances.