The objective of this study was to determine the effect of hypercholesterolemia on the transarterial wall oxygen gradient. Female New Zealand white rabbits (3-4 kg) were fed a 0.5% cholesterol supplemented diet or a 0.25% cholesterol supplemented diet and their transarterial wall oxygen gradients measured prior to the formation of atherosclerotic lesions at 4 weeks (0.5% cholesterol group) or 8 weeks (0.25% cholesterol diet) after beginning the diet. Arterial blood oxygen content and arterial blood pressure were recorded during the experiments. Control rabbits had a serum cholesterol level of 52.8 ± 6 mg/dl, rabbits fed the 0.25% cholesterol diet had serum cholesterol levels of 579.5 ± 29.2 mg/dl, and those fed the 0.5% cholesterol diet had serum cholesterol levels of 1235.4 ± 37.6 mg/dl. There was no difference in the transarterial wall oxygen gradients between any of the groups. These results were noted with no differences in arterial blood oxygen content, arterial blood pressure, or evidence of atherosclerotic lesions. Hypercholesterolemia does not alter the delivery of oxygen to the artery wall prior to the formation of atherosclerotic lesions.