Platelet adherence and aggregation are important in the development of ischemic sequelae in atherosclerosis. To directly examine platelet interaction with plaque, everted, deendothelialized aortic fibrous plaques from Watanabe-heritable hyperlipidemic rabbits were exposed to flowing human blood in an annular perfusion chamber. Morphometry was used to compare platelet adherence and thrombi on this surface with that observed when blood was perfused over normal New Zealand White (NZW) rabbit aortic subendothelium. Platelet spreading, adherence, and thrombi on the atherosclerotic surface were approximately half that observed on NZW aorta. When surface proteins of NZW aorta were denatured by a hot-tip catheter, these parameters were reduced by 89-96%. The reduced thrombogenicity of uncomplicated plaques may help keep these narrowed vessels patent, while fissure, rupture, or hemorrhagic dissection of plaque may precipitate occlusive thrombosis.