Treatment of atherosclerosis has focused mainly on decreasing low-density lipoprotein cholesterol (LDL-C). However, recent coronary angiography trials have revealed that aggressive lowering of LDL-C below 100 mg/dl arrests atherosclerosis progression in only 50% to 60% of patients. Furthermore, with quantitative coronary angiography, significant regression occurred only in advanced fibrous-fatty plaques (> or = 50% stenosis) and not in the younger, more cell-proliferative lesions (< 50% stenosis). It is clear that lipid-lowering therapy has limited efficacy; therefore, other drugs, especially antiproliferative agents, may be useful for secondary and primary prevention. To test this hypothesis a new calcium antagonist, amlodipine, which has in vitro antiproliferative, cell membrane stabilizing, and antioxidative properties, was studied to determine whether it has antiatherogenic effects in nonhuman primates. Amlodipine normalized elevated levels of oxidized arterial cholesterol without reducing elevated total plasma cholesterol levels and significantly suppressed atherosclerosis progression in monkeys who had been fed an atherogenic diet. These data suggest that amlodipine may be an excellent candidate, in combination with lipid-lowering drugs, for dual therapy of atherosclerotic vascular disease, and also may be effective monotherapy, even when LDL-C is not lowered satisfactorily.