Background-Angiography of the coronary arteries reflects only changes in luminal dimensions. With intravascular ultrasound, cross-sectional images can be obtained and area measurements can be added to calculate volumes of the external elastic membrane (EEM), plaque plus media (P+M), and lumen. The aim of this study was to investigate the effect of lipid lowering by simvastatin on coronary atherosclerotic P+M as changes in volumes of EEM, P+M, and lumen. Methods and Results-In 40 male patients with hypercholesterolemia, ischemic heart disease, and a nonsignificant coronary artery lesion in a not previously revascularized coronary artery, serial intravascular ultrasound studies with an ECG-triggered pullback were performed at baseline, after 3 months on a lipid-lowering diet, and after another 12 months on simvastatin 40 mg/d. Mean length of the analyzed atherosclerotic segments was 5.9 +/- 3.3 mm. After 12 months on simvastatin, a significant reduction in P + M volume of 6.3% (P = 0.002) was observed, whereas only a nonsignificant reduction in EEM volume of 1.8% was seen without any concomitant change in lumen volume. A significant reduction in total cholesterol of 31.0% (6.1 +/- 0.8 versus 4.2 +/- 0.7 mmol/L, P<0.001) and LDL cholesterol of 42.6% (4.0 +/- 0.8 versus 2.2 +/- 0.6 mmol/L, P<0.001) was obtained. Conclusions-Lipid-lowering therapy with simvastatin for 12 months is associated with a significant P + M regression in coronary arteries measured as reduction in P + M and EEM volumes without any concomitant change in lumen volume.