We administered a high cholesterol diet to racing greyhounds and studied its effects on the characteristics of carotid sinus reflex control of arterial pressure-flow relations. Dogs were anesthetized with halothane, and pressure and flow were simultaneously measured in the ascending aorta and the celiac, mesenteric, renal, and iliac arteries. The carotid sinuses were isolated bilaterally and perfused with a physiological salt solution under controlled conditions. The variation of regional pressure-flow relations and regional vascular resistance was assessed as a function of mean carotid sinus pressure (MCSP) with the vagi bilaterally sectioned to eliminate aortic arch afferents. Some differences were found in set point (i.e., MCSP = mean arterial pressure) values of hemodynamic variables; cardiac output and renal and iliac flows were significantly lower. Control and set point values of mean arterial pressure were not significantly different between the two groups. The variation of every hemodynamic variable with the exception of heart rate with carotid sinus pressure was attenuated markedly in the diet-treated dogs. Substantial lesions were found involving the entire carotid sinus region of every diet-fed animal. These results suggest that pathological alterations in the carotid sinus region are at least in part responsible for a reduction in the sensitivity of carotid sinus baroreflexes associated with atherosclerosis. Circ Res 46: 237-244, 1980