1. Two experiments were conducted to determine whether or not high dietary levels of vitamin E affect the development of atherosclerotic lesions in aortas of cholesterol-fed (5 g/kg diet) rabbits that were mechanically deendothelialized by balloon catheterization.
2. In the first experiment, the aortas of rabbits fed 2000 mg vitamin E/kg diet (i.e. 50-fold their nutritional requirement) for 8 weeks showed no gross morphological differences, either within or outside experimentally damaged areas, from those of rabbits fed the nutritionally adequate control level (40 mg/kg) of the vitamin.
3. In the second experiment, rabbits fed 10000 mg vitamin E/kg diet (i.e. 250-fold requirement) for 14–15 weeks showed significantly greater endothelial loss and plaque formation at aortic sites outside of the mechanically damaged area than did controls. Plasma cholesterol levels were very high (9000–14000 mg/1) and were not affected by dietary vitamin E level until 10–12 weeks when they were reduced moderately (18%).
4. It is concluded that very high levels of vitamin E can potentiate spontaneous atherosclerotic lesions, and it is suggested that this effect may depend on high cholesterol status.