Pre-existing collateral vessels provide an alternative route for blood flow following acute arterial occlusion. 2. In a novel model of acute arterial occlusion in the isolated rabbit ear vascular bed the development and maintenance of collateral perfusion has an obligatory dependence on endothelium-derived relaxing factor (EDRF) activity. 3. This endothelium-dependent mechanism is severely impaired in dietary-induced hypercholesterolaemia, leading to substantially reduced collateral perfusion. 4. Collateral perfusion may also be influenced by vasodilators, specifically in the rabbit ear model the potassium channel opener BRL 38227 greatly enhances perfusion, sodium nitroprusside (an exogenous analogue of EDRF) has early but limited beneficial effects while verapamil is without effect.