To study the role of endogenous adenosine in coronary dilatation induced by beta-adrenergic stimulation, isolated rat hearts were perfused at a constant flow rate. Perfusion of the heart with isoproterenol caused increases in the heart rate, left ventricular developed pressure, coronary dilatation, and release of adenosine and its degradation products. Theophylline inhibited isoproterenol-induced coronary dilatation without any significant effects on other contractile properties such as heart rate and left ventricular developed pressure. Coronary dilatation induced by exogenous adenosine was also inhibited by theophylline. These results suggest that beta-adrenergic stimulation induces coronary vasodilatation not only through direct beta-adrenergic responses, but also through increases in extracellular adenosine.