Pulse ischemia-dependent submaximal increase in adenosine levels in plasma and in the interstitium is believed to mediate the phenomenon of ischemic preconditioning of the heart, by the interaction with the specific A1 and A3 receptors on myocytes. The aim of the study was to evaluate the effects of chronic oral treatment with dipyridamole (75 mg twice a day for 5 days) in coronary artery disease (CAD) patients with positive echocardiographic stress test with high-dose dipyridamole (DET). We evaluated positivity to DET, adenosine plasma levels in 12 patients treated with dipyridamole in comparison to eight patients treated with placebo. After oral administration of dipyridamole we observed a significant reduction in the number of patients positive to DET (5/12; P=0.02), a pulse increase in adenosine plasma levels (from 220+/-55 to 450+/-70 nmol/l), without any significant haemodynamic effects. Our results suggest that dipyridamole, administered orally at a low dose, but sufficient to increase adenosine plasma level, was able to prevent myocardial ischemia induced by high-dose dipyridamole echo-stress test in CAD patients.