Dutch-belted rabbits fed a 2% cholesterol diet for 8 weeks developed atherosclerotic lesions that covered 37.2% +/- 3.5% of the aortic luminal surface. In samples of aortic arch, accumulation of cholesterol and triglyceride was also observed. Oral administration of nicardipine or nifedipine at dosages of 40 mg/kg twice daily for 8 weeks reduced plaque area by 49.2% and 58.7%, respectively. Nicardipine and nifedipine reduced cholesterol accumulation in the aortic arch by 74.5% and 69%, respectively. Triglyceride accumulation was totally abolished. Neither drug significantly altered cholesterol concentration of plasma low density lipoprotein or high density lipoprotein, although nicardipine produced a 42% reduction in cholesterol concentration of the d less than 1.006 g/ml fraction. The above results suggest potential therapeutic utility of nicardipine in atherosclerosis.