We investigated myocardial 1C-palmitate clearance kinetics at a resting heart rate (control) and during pacing using positron-emission tomography in 10 patients with significant coronary artery stenosis (>70%) and evidence of exercise-induced ischemia. Serial 1C-palmitate images acquired at control and during pacing revealed biexponential myocardial 11C clearance both in myocardium supplied by a stenotic coronary artery (myocardium “at risk”) and in myocardium supplied by a normal coronary artery (normal myocardium). At control, the average rate of myocardial 11C clearance from the early rapid curve component (the clearance half-time) was similar in normal myocardium and in that at risk (22.2 + 5.2 vs 21.0 + 5.4 min, NS), as was the amount of myocardial '`C activity at the end of the early rapid phase (residual fraction 56.3 ± 7.2% vs 54.7 ± 7.3%, NS). Thus, myocardial clearance was homogeneous at control, suggesting a similar rate and amount of 1'C-palmitate oxidation in normal myocardium and in that at risk. Pacing shortened clearance half-times and decreased residual fraction in both normal myocardium and that at risk compared with control. However, clearance halftimes were 17% longer and residual fractions 14% higher in myocardium at risk compared with normal myocardium (p < .005 and p < .01, respectively). Therefore, during pacing myocardial 1'C clearance became heterogeneous, suggesting impaired 11C-palmitate oxidation in myocardium at risk compared with normal myocardium. Increased substrate utilization in response to increased workload can be thought of as a measure of metabolic reserve. Our data suggest metabolic reserve for free fatty acid oxidation is impaired in myocardium supplied by a significantly stenosed coronary artery and that this impairment can be detected by analysis of myocardial 1C-palmitate clearance.