Atherosclerotic lesions of aorta and arteries were induced in guinea pigs fed a diet supplemented with 1% cholesterol and vitamin D2 (0.75 million IU/kg of diet) for 6 weeks. Histopathological observation revealed intimal proliferation and calcification of the intima and media, but no atheroma was present at the sites of arterial injury. However, the biochemical findings revealed accumulation of cholesterol, mainly esterified, and calcium in the aorta. Significant correlation between the calcium and phosphorus contents in the aorta indicates the presence of a probable calcium-phosphate complex. Synergism for the induction of atherosclerotic lesions was shown between high cholesterol and excess vitamin D2. Sodium 4-(hexadecylamino)benzoate (cetaben) (90 mg/kg/day, p.o.) and trisodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) (5 mg/kg/day, s.c.) inhibited the development of atherosclerotic lesions induced in this manner. These effects were associated with a significant reduction of serum and aortic cholesterol levels and a significant elevation of HDL-cholesterol levels caused by cetaben, and a significant reduction in aortic calcium caused by EHDP. These two drugs and clofibrate, however, had no significant effect on the regression of pre-established atherosclerotic lesions.