Mental and emotional arousal are known to trigger coronary events. The relation between hypercholesterolemia, behavioral factors, and mental stress-induced alterations in endothelial function are not well defined. Flow-mediated brachial arterial vasodilation has been established as a measure of arterial endothelial function. High-resolution ultrasound was used to measure mental stress-mediated, flow-mediated, and the combination of mental stress- and flow-mediated brachial artery dilation in 38 subjects, 20 of whom had total cholesterol levels > or =200 mg/dl. Mental stress was provoked by anger recall and mental arithmetic and trait hostility were assessed using the Cook-Medley scale. Under mental stress, participants with hypercholesterolemia showed less vasodilation than participants without hypercholesterolemia, even after adjustment for age and the magnitude of blood pressure response to mental stress. Mental stress attenuated flow-mediated brachial arterial vasodilation. There was an inverse relation between hostile affect and percent change in brachial artery diameter after mental stress combined with hyperemia (r = -0.57, p <0.001). Thus, hypercholesterolemia is associated with impaired vasodilation in response to mental stress. Mental stress inhibits flow-mediated vasodilation in normal subjects and those with hypercholesterolemia. The magnitude of this inhibition is associated with hostility.