Modified Watanabe heritable hyperlipidemic rabbits (M-WHHL) were fed either standard rabbit diet or diet supplemented with 0.5% wt/wt of the lipophilic antioxidant vitamin E (d,l-alpha-tocopherol). Animals of 10-12 weeks of age were divided into two groups matched for distribution of serum cholesterol levels at the beginning of the 12 week study period. A significant hypocholesterolemic response to vitamin E feeding was observed throughout the study. Vitamin E supplementation increased serum vitamin E levels approximately fourfold and restricted ex-vivo copper mediated oxidative modification of low density lipoprotein (LDL) as quantitated by fluorescence at 430 nm. Post mortem examination of aortic tissue revealed a significant (32%) inhibition of surface area lesion involvement in the arch region as determined by image analysis. It is concluded that administration of vitamin E to M-WHHL rabbits brings about a significant hypocholesterolemic response, confers on LDL significant protection against oxidative modification and either or both contribute to the inhibition of early aortic lesion development.