Numerous experimental studies have reported that common antihypertensive drugs such as diuretics, beta-blockers, and methyldopa have adverse effects on plasma lipids and lipoproteins. The present study was designed to define the effect of clentiazem (10 mg/kg/day) an antihypertensive drug, on hyperlipidemia in rabbits on a cholesterol-rich diet (1%) for 12 weeks. Compared with controls, clentiazem treated rabbits had lower plasma concentrations of triglycerides (55%), total cholesterol (24%), free cholesterol (27%), esterified cholesterol (23%) and phospholipids (24%). The decrease in cholesterol was accounted for by a reduction of VLDL-cholesterol (13%), IDL-cholesterol (24%) and primarily LDL-cholesterol (45%). Neither HDL-cholesterol nor chemical composition of VLDL, IDL, LDL and HDL was altered. When the aortic atherosclerotic involvement was evaluated by computerized planimetry, a 24% reduction of lesions was noted in clentiazem treated animals (P less than 0.05). Similarly, cholesterol content extracted from aortic wall was decreased. Our data therefore demonstrated that clentiazem is a potential antiatherosclerotic agent capable of decreasing plasma lipids and atherogenic lipoproteins as well as aortic fatty streaks.