In patients with myocardial infarction, left ventricular sympathetic denervation exceeds the size of the scar tissue. However, little is known about the regional innervation in patients with coronary artery disease (CAD) but no myocardial infarction. Using positron emission tomography (PET) with N-ammonia and C-hydroxyephedrine (HED), resting perfusion and presynaptic sympathetic innervation were studied in eight patients (seven males, one female; 58+/-9 years) with multi-vessel CAD and no history of myocardial infarction. Using polar map analysis of the PET data, the results were regionally compared with normal databases. The mean HED retention was 8.0%+/-2.0% x min(-1). Myocardial resting perfusion was normal in 23 of 24 vascular territories. Despite normal resting perfusion, significantly reduced HED retention, indicating dysinnervation, was found in 14 of 23 (61%) vascular territories (six of eight patients). Of the dysinnervated territories, 11 (79%) showed angiographically severe stenosis (>or=90% of native vessel/coronary artery bypass graft), eight (57%) showed ischaemia (myocardial perfusion scintigraphy/stress-electrocardiogram) and 12 (86%) had been revascularized. Of the nine segments with normal innervation, two (22%) revealed severe stenosis, two (22%) showed ischaemia and seven (78%) had been revascularized. It can be concluded that, in patients with advanced CAD and normal left ventricular function, dysinnervation can occur in the absence of myocardial infarction. This is consistent with the hypothesis that sympathetic neurones are more susceptible than myocytes to ischaemic damage.