Fibromuscular intimal thickening was seen in the ascending and thoracic aorta of the swine fed 62,500 IU of vitamin D3/kg of diet for three months duration; and after 3 months of vitamin D3withdrawal, atherosclerotic lesions were found. In rabbits, pronounced aortic smooth muscle cell necrosis developed with the forced feeding of 10,000 IU vitamin D3dissolved in corn oil/kg body weight/day for 14 days. Serum analyses indicated that blood calcium did not differ from that of animals fed corn oil alone, but that the level of serum 25‐hydroxy‐ vitamin D3measured by HPLC was 30 times that in the control animals. These data suggest that choleclaciferol (the oxidized sterol with vitamin D3activity) has a very destructive influence on the integrity of arterial wall, and that smooth muscle cell necrosis could be caused by enhanced membrane permeability to Ca2+following 25‐hydroxy‐vitamin D3incorporation into smooth muscle cell me