Positron emission tomography (PET) with C-11 acetate allows noninvasive quantification of myocardial oxidative metabolism. To assess the myocardial metabolic reserve, clearance of C-11 acetate from the myocardium was measured with PET in 8 normal subjects at rest and during the infusion of dobutamine (inotropic agent) or dipyridamole (vasodilator). During dobutamine infusion, the clearance rate constant of C-11 acetate increased significantly (0.063 +/- 0.014 vs 0.109 +/- 0.016, p < 0.002) in good correlation with the rate-pressure product (r = 0.83). During dipyridamole infusion, myocardial acetate clearance also significantly increased (0.088 +/- 0.024, p < 0.05) in correlation with the rate-pressure product (r = 0.54). In normal myocardium, myocardial oxidative metabolism increased in response to increased work load with pharmacological stress. These findings suggest that PET with C-11 acetate and pharmacological stress may be a promising approach for the evaluation of metabolic reserve in patients with ischemic heart disease.