Experimental studies indicated the clearance rate constant of 11C-acetate as an index of regional myocardial oxygen consumption. To assess the response of the clearance rate from the left ventricular (LV) myocardium to the change in plasma substrate levels and to the increase in the cardiac work load in normal subjects, a total of 18 dynamic positron emission tomographic studies were performed at rest in the fasting state (control) (n = 7), after oral glucose administration (n = 4), and during dobutamine infusion (n = 7) in 7 normal volunteers. The clearance rate constant (Kmono) was similar in the control (0.065 +/- 0.017 min-1) and glucose loading states (0.059 +/- 0.008 min-1), whereas a significant increase in Kmono was observed during dobutamine infusion (0.106 +/- 0.018 min-1) (p < 0.01) in relation to the increase in the pressure-rate product with a correlation coefficient of 0.873 (p < 0.01). When the LV myocardium was divided into 6 segments, there were no significant differences among the segments in Kmono values in any condition. These normal responses should be valuable for assessing oxidative metabolic reserve and regional changes in oxidative metabolism in patients with coronary artery disease.