Pravastatin has been shown, in an experimental model of ischemia reperfusion, to increase adenosine levels, which exert a potent and protective effect on the heart. The purpose of this study was to investigate whether pravastatin can provide cardioprotection by increased production of adenosine in patients undergoing coronary angioplasty, a clinical model of ischemia reperfusion. Thirty-five hyperlipidemic patients who underwent elective angioplasty for a major epicardial coronary artery were randomly allocated to either 3-month pravastatin or placebo before catheterization. In the placebo group, the mean ST-segment shift during the second balloon inflation was similar that observed during the first inflation, whereas in the preconditioned patients, the shift was significantly less, which is consistent with ischemic preconditioning. In the pravastatin-treated patients, the changes of ST-segment shift were similar between the first and second balloon inflations. In constrast, the patients who received aminophylline developed higher ST-segment shifts during the first and second inflations than those in the pravastatin-treated group alone. Measurements of chest pain score and myocardial lactate extraction ratios during inflation mirrored those of the ST-segment shift. The present study demonstrates that administration of pravastatin results in a significant gain in tolerance to ischemia during angioplasty. The effect of pravastatin was abolished by aminophylline, suggesting that the cardioprotective effect of pravastatin may result from activation of adenosine receptors.