OBJECTIVE: This review discusses the phenomenon of ischaemic preconditioning and its potential application to cardiac surgery. The biology of ischaemic preconditioning is explained and the more limited evidence suggesting that the human heart can be preconditioned is discussed. METHODS AND RESULTS: It is now accepted that the heart is capable of short-term rapid adaptation in response to brief ischaemia so that during a subsequent, more severe ischaemic insult myocardial necrosis is delayed-ischaemic preconditioning. The infarct-delaying properties of ischaemic preconditioning have been observed in all species studied. Five minutes of ischaemia is enough to initiate preconditioning and the protective period lasts for 1-2 h. Laboratory experiments have demonstrated that the stimulation of adenosine receptors initiates preconditioning and the intracellular signal transduction mechanisms involve protein kinase C and ATP-dependent potassium channels, although there may be some differences between species. An analysis of studies on myocardial infarction in humans has revealed that some patients reporting angina in the days before infarction have a better outcome and this may be due to the ischaemia causing preconditioning. More direct evidence has come from an investigation of patients undergoing percutaneous transluminal angioplasty in whom the ST-segment changes induced by balloon inflation were more marked during the first inflation than the second. In patients undergoing coronary artery bypass grafting the decline in ATP content during the first 10 min of ischaemia was reduced in patients subjected to a brief preconditioning protocol. CONCLUSIONS: Preconditioning is a powerful and reproducible method of protecting the myocardium from irreversible ischaemic injury. There is now evidence indicating that the human heart can be preconditioned. However, more trials are necessary in patients undergoing cardiac surgery before the role of preconditioning as a means of myocardial protection can be assessed.