Regional reductions in norepinephrine-tracer uptake are found in pigs with hibernating myocardium. Clinical studies would suggest that this is evidence for denervation; however, the functional responses to sympathetic stimulation have not been evaluated, and our previous studies with -adrenergic stimulation have not suggested denervation hypersensitivity. Therefore, pigs were chronically instrumented to produce hibernating myocardium characterized by chronic regional dysfunction, and histological viability. Open-chest studies were performed to determine changes in regional function in response to both pre- and post-junctional stimulation. Regional segment shortening was reduced at rest in hibernating myocardium as compared to controls (13±3% vs. 27±3%, p=0.004). During stellate ganglion stimulation regional function increased in both groups of animals (p=0.008 vs. baseline) , but the increase in hibernating myocardium was blunted as compared to controls (%, 3±2% vs. 8±3%, p=0.04). Similar results occurred with intracoronary tyramine (10 mcg/kg). Functional improvement during intravenous epinephrine infusion (0.35 mcg/kg/min) was also blunted in hibernating myocardium compared to controls (%, 7±1% vs. 15±2%, p=0.04). Even when the improvement in function was expressed relative to the reduced baseline, there was no evidence for catecholamine-mediated hypersensitivity in hibernating myocardium. We therefore conclude that functional responses to both pre- and post-junctional sympathetic stimulation are blunted in pigs with hibernating myocardium. In contrast to previous studies of infarcted, denervated and acutely stunned myocardium, there is no catecholamine-induced hypersensitivity in hibernating myocardium. These data suggest a down-regulation in functional responses to stimulation that would protect hibernating myocardium from demand-induced ischemia at the expense of contractile reserve during sympathetic stimulation.