Mice deficient in apolipoprotein E (apoE) become hypercholesterolaemic and suffer atherosclerosis of the large arteries. The severity of the atherosclerosis is exacerbated by feeding a diet enriched in fat and cholesterol, which also causes the development of unstable lesions at certain sites of predilection. The instability manifests as spontaneous plaque rupture with the formation of mural thrombus, which in some cases is large enough to occlude the vessel. Amongst the affected vessels are the coronary arteries: some fat-fed apoE knockout mice suffer myocardial ischaemia and infarction in consequence. Analysis of the physiological properties of such ischaemically diseased hearts shows that they have a significantly greater resistance to reperfusion injury than age- and diet-matched wild-type controls.