Coronary endothelial function is impaired in hypertension; however, the severity of this impairment varies among patients. We aimed to identify the predictors of coronary endothelial dysfunction among clinical variables related to hypertension and atherosclerosis. Twenty-seven untreated, uncomplicated essential hypertensive patients and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using (15)O-water positron emission tomography (PET) at rest and during a cold pressor test (CPT). Coronary vascular resistance (CVR) during CPT was used as a marker of coronary endothelial function. Serum low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, malondialdehyde-LDL, homeostasis model assessment, high-sensitivity C-reactive protein (hs-CRP), and plasma interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were also measured. CVR during CPT was significantly higher in hypertensive patients than in healthy controls (114+/-26 vs. 94+/-12 mmHg/[mL/g/min]; p<0.05). By univariate analysis, CVR during CPT was correlated with LDL cholesterol (r=0.38, p<0.05), IL-6 (r=0.46, p<0.02), and TNF-alpha (r=0.39, p<0.05) in hypertensive patients. By multivariate analysis, IL-6 and TNF-alpha were significant independent predictors of CVR during CPT. Elevated plasma IL-6 and TNF-alpha levels were independent predictors of coronary endothelial dysfunction in hypertensive patients. These results suggest that plasma IL-6 and TNF-alpha might be useful for identifying the high risk subgroup of hypertensive patients with coronary endothelial dysfunction and provide an important clue to link systemic inflammation to the development of coronary atherosclerosis.