It is unclear whether the protection observed in human heart following repetition of brief episodes of ischaemia is due to opening of coronary collaterals or to ischaemic preconditioning. We investigated whether the improvement in ST segment change following repeated episodes of brief ischaemia during coronary angioplasty is due to preconditioning when the size of the area at risk and the collateral flow are taken into account. Thirty-six patients underwent percutaneous transluminal coronary angioplasty. Intracoronary ST segment changes were measured throughout the procedure and used as an endpoint. The size of the area at risk and the collateral perfusion within the ischaemic bed were measured using single photon emission computerized tomography(SPECT). Mean ST segment shift observed in all patients significantly decreased from 11.0±2.6 mm during the first balloon inflation to 8.5±2.3 mm during the second inflation. This protective effect occurred in the absence of any change in the size of the area at risk(mean: 46±5%of LV) and of the collateral perfusion to the ischaemiczone (mean: 23±4%of flow in the non-ischaemic zone). These results suggest that ischaemic preconditioning does occur during repeated brief coronary artery occlusion in the human heart. It is unclear whether the protection observed in human heart following repetition of brief episodes of ischaemia is due to opening of coronary collaterals or to ischaemic preconditioning. We investigated whether the improvement in ST segment change following repeated episodes of brief ischaemia during coronary angioplasty is due to preconditioning when the size of the area at risk and the collateral flow are taken into account. Thirty-six patients underwent percutaneous transluminal coronary angioplasty. Intracoronary ST segment changes were measured throughout the procedure and used as an endpoint. The size of the area at risk and the collateral perfusion within the ischaemic bed were measured using single photon emission computerized tomography (SPECT). Mean ST segment shift observed in all patients significantly decreased from 11.0 ± 2.6 mm during the first balloon inflation to 8.5 ± 2.3 mm during the second inflation. This protective effect occurred in the absence of any change in the size of the area at risk (mean: 46 ± 5% of LV) and of the collateral perfusion to the ischaemiczone (mean: 23 ± 4% of flow in the non-ischaemic zone). These results suggest that ischaemic preconditioning does occur during repeated brief coronary artery occlusion in the human heart.