The effect of a cholesterol enriched diet on concentration responses to 5-hydroxytryptamine, ergometrine, and acetylcholine and on endothelium dependent relaxation was investigated in rabbit aortic strip preparations. Sensitivity to ergometrine was slightly reduced after both two and 10 weeks of cholesterol feeding. Sensitivity to 5-hydroxytryptamine was slightly reduced after two but not after 10 weeks of cholesterol feeding. Sensitivity to acetylcholine was not altered at two or 10 weeks in the absence of endothelium, but the endothelium dependent lowering of the constrictor concentration-response was almost abolished after 10 weeks of cholesterol feeding. Likewise the endothelium dependent relaxant response of preconstricted preparations to acetylcholine was almost abolished after 10 weeks of cholesterol feeding. Thus this model of hyperlipidaemia leads after 10 weeks to loss of endothelium dependent relaxation.