Reduced arterial compliance is associated with arteriosclerosis. In some arteries, this is due in part to abnormal vascular tone, which can be altered by low-density lipoprotein (LDL) cholesterol reduction and statin therapy. We tested the effectiveness of statin therapy in improving arterial compliance in patients with manifest coronary disease (CAD) and/or diabetes. Simvastatin (40 mg/day) was administered to 10 patients with proven CAD for 4 months. As measured by air plethysmography, compliance of the arterial segments in the thigh improved in every patient after 2 months, increasing by 34% by the fourth month. Compliance at the calf was not affected. These results suggest that compliance in the thigh is controlled by smooth muscle tone. Compliance measurements in the thigh and calf may be a useful measurement in evaluating high-risk patients and monitoring cholesterol-lowering therapy.