We tested the hypothesis that coronary reactive hyperemia following a single brief diastolic occlusion and subsequent systole is coupled to myocardial metabolic activity and myocardial O2 consumption (MVO2). Sixteen conscious dogs with Formalin-induced heart block were studied. A 400-ms diastolic occlusion was introduced during normal ventricular pacing, resulting in a reactive hyperemic repayment of 216 +/- 22%. A 400-ms diastolic occlusion was also introduced during a higher level of myocardial metabolic activity induced by ventricular paired pacing. MVO2 and mean coronary blood flow were significantly increased relative to these parameters during normal pacing, but reactive hyperemic repayment (189 +/- 18%) was not significantly changed. A third set of conditions was designed to measure the response to a 400-ms occlusion during normal pacing while eliminating the difference in magnitudes of myogenic influences that may exist between paired pacing and normal pacing. Adenosine and phenylephrine were infused intravenously during normal pacing to maintain mean aortic pressure and mean coronary flow at paired pacing levels. MVO2 was similar to O2 consumption during normal pacing in the absence of drug infusion, but the reactive hyperemic repayment was significantly reduced (94 +/- 22%) relative to paired pacing. Thus the magnitude of reactive hyperemic response after a brief diastolic occlusion is related primarily to myocardial metabolic activity.