In this pilot study, 12 patients (6 men, 6 postmenopausal women) with hypercholesterolemia were treated with low-dose (5 mg/d) simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, for 4 weeks. Low-density lipoprotein (LDL) samples were isolated at the beginning (week 0) and at the end (week 4) of the treatment regimen. Simvastatin caused significant decreases of total cholesterol (-18.1%), LDL cholesterol (-27.6%), and apolipoprotein B (-21.8%), and significantly reduced total cholesterol, free cholesterol, cholesterol esters, phospholipids, and protein in LDL without significantly changing the component ratios and fatty acid levels of LDL. However, simvastatin therapy had no major effects on either antioxidant levels in LDL or the oxidative susceptibility of LDL. We conclude that low-dose simvastatin significantly reduces LDL cholesterol levels without increasing the oxidative susceptibility of LDL or decreasing the antioxidant levels of LDL, and thus may reduce the risk of coronary artery disease.