Male rabbits were injected intraperitoneally for five consecutive days with one of the following: (A) 0.3 ml/kg dimethyl ethylene glycol (solvent); (B) 40 mg/kg cholesterol and 8 mg/kg ergocalciferol in solvent; (C) same regimen as B with the addition of 150 mg/kg ascorbic acid in water. Daily blood samples were taken for determination of cholesterol and triglycerides, and for lipoprotein electrophoresis. After 5 days of injections, histological sections were made of the aorta at the arch. After 5 days, group B, as compared with group A, had higher serum cholesterol (150 ng/dl vs. 50 mg/dl, p less than 0.005), higher serum triglycerides (650 mg/dl vs. 150 mg/dl, p less than 0.01), and lower high-density lipoprotein (16% vs. 35%, p less than 0.05). On autopsy, discontinuous elastic fibers and intimal damage were seen in sections of the aortas from group B, but not from group A. After 5 days, group C had control levels of cholesterol (55 mg/dl) and triglycerides (160 mg/dl), and no significant difference from the control lipoprotein profile. Injections of cholesterol alone showed a slight induction of aortic lesions and blood chemistry changes. No alterations in these parameters were induced by ergocalciferol alone. The data indicate a prophylactic effect of vitamin C on the biochemical and histological changes rapidly induced by cholesterol and ergocalciferol.