Study objective - The aim was to determine whether high dose dietary vitamin E could improve myocardial resistance to ischaemia and reperfusion. Vitamin E is an important physiological antioxidant which can be accumulated to high levels in the myocardium, without toxicity, by chronic dietary supplementation. Design - Subjects were fed a standard laboratory feed and water ad libitum for 10 d, plus either d-alpha-tocopoheryl acette 200 IU.kg-1.d-1 orally (vitamin E group), or no supplement (control group). The animals then underwent either 60 or 180 min of left anterior descending coronary artery ligation, followed by 6 h reperfusion. The area at risk was identified by colloidal carbon, and necrosis by triphenyl tetrazolium chloride and light microscopy. Subjects - Studies were performed on New Zealand white rabbits weighing approximately 3.5 kg. Measurements and main results - In the 60 min ligation study, the control group had 30.5 (SD 4.0)% necrosis of the area at risk but the vitamin E group had no necrosis (n = 5 per group, p greater-than-or-equal-to 0.0001). In the 180 min ligation study, the control group had 74.1 (11.5)% necrosis of the area at risk whereas the vitamin E group had 23.1 (7.2)% (n = 5 per group, p greater-than-or-equal-to 0.0001). Conclusions - High dose dietary supplementation with vitamin E can improve myocardial tolerance to ischaemia and reperfusion, significantly reducing myocardial infarct size.