Clinical and experimental evidence suggests that hypertrophied myocardium is more susceptible to injury from ischaemia than normal myocardium. This study was designed to investigate whether preconditioning confers protection on hearts with moderate hypertrophy. Cardiac hypertrophy induced by hypertension was produced in rats by giving saline drinking fluid and subcutaneous deoxycorticosterone acetate for four weeks. After thoracotomy, localisation of the left main coronary artery and stabilisation, groups of hypertensive animals with cardiac hypertrophy (HT) and their age matched normotensive controls (NT) underwent a preconditioning protocol consisting of 5 min occlusion of the left main coronary artery followed by 10 min reperfusion. This was followed by 45 min ischaemia and at least 2.5 h reperfusion. Control animals in the hypertrophied and normotensive groups were treated identically but were not subjected to the preconditioning protocol. Thus there were four experimental groups: HT preconditioned (n = 8), HT control (n = 7), NT preconditioned (n = 7), and NT control (n = 7). Infarct size was measured using triphenyl tetrazolium chloride and was expressed as a percentage of the volume at risk, measured with fluorescent particles. Heart weight was greater (p < 0.01) in the HT groups than in the NT groups [HT preconditioned 1.7(SEM 0.06) g, HT control 1.71(0.02) g, NT preconditioned 1.3(0.04) g, NT control 1.31(0.03) g]. Infarct to risk volume ratio (I/R) was significantly lower (p < 0.05) in the preconditioned groups as compared with controls [HT preconditioned 19.1(1.5)% v HT control 67.1(5.6)%, and NT preconditioned 33.4(5.5)% v NT control 77.1(3.8)%]. There was no significant difference in the volume at risk of infarction between the four groups. Ischaemic preconditioning can induce myocardial protection in hypertrophied myocardium; this is the first study to demonstrate preconditioning in hypertrophy.