Ischaemic preconditioning has not been demonstrated to reduce infarct size following global ischaemia in murine myocardium. Eighteen mouse hearts were isolated, perfused in the Langendorff mode, and randomised to control or preconditioning groups. Preconditioned hearts received four periods of five minutes global ischaemia with five minutes of intervening reperfusion. Control hearts were perfused normally during this period. Both groups were then subjected to 30 minutes global ischaemia followed by 30 minutes reperfusion. Infarct size, contractile recovery and LDH leakage were assessed. Mean infarct size was reduced from 57% of ventricular volume (controls) to 33% in preconditioned hearts (P = 0.003). A small improvement in contractile recovery was also observed (6.3% of baseline in controls, 15.5% in preconditioned hearts; P = 0.004). Release of LDH did not differ significantly between groups. This study confirms for the first time that ischaemic preconditioning can delay the onset of myocardial necrosis following global ischaemia in the isolated mouse heart.