In closed-chest anaesthetized dogs, aminophylline was infused into the left circumflex coronary artery at a rate of 250 μg/min. When the heart rate was lower than 100 beats/min, infusion did not modify the left circumflex coronary blood flow and resistance. When the heart rate was elevated to an average of 153 ± 6 beats/min by right atrial pacing, infusion inhibited the increase in left circumflex coronary blood flow and decrease in coronary resistance. The pacing-induced increment in coronary blood flow was reduced by an average of 64% and the flow deficit was associated with a lowering of the coronary sinus blood oxygen tension. Since aminophylline is known to inhibit the coronary dilator action of exogenous adenosine, the results support the concept that adenosine resulting from the breakdown of adenine nucleotides is a mediator of the metabolic regulation of coronary blood flow.