To determine the morphological bases of thallium-201 myocardial distribution in chronic cardiac dysfunction and their relation to myocardial blood flow, myocardial slices from ten excised hearts of five chronic ischaemic heart disease patients and five idiopathic dilated cardiomyopathy patients, were imaged on a gamma camera to quantitate the uptake of thallium-201, injected 4 h before surgery, and myocardial blood flow from distribution of technetium-99m-labelled human albumin microspheres injected during surgery. Tracer distribution was correlated with histologically assessed myocardial fibrosis and myocytolysis. Thallium-201 uptake was inversely related to fibrosis (r = -0.73, in ischaemic heart disease, r = -0.65 in idiopathic dilated cardiomyopathy). In ischaemic heart disease, myocardial blood flow was related neither to thallium-201 uptake (r = 0.41) nor to the extent of fibrosis (r = -0.48). In this group, segments with normal or mildly reduced thallium-201 uptake showed significantly lower fibrosis than those with moderate or severe uptake defects (5 +/- 7% and 7 +/- 11% vs 33 +/- 14% and 42 +/- 12%, respectively, P < 0.0001. In a clinical model of chronic ischaemic dysfunction, despite severely depressed myocardial blood flow, extensive areas of myocardium devoid of significant structural impairment are present. Thallium-201 uptake effectively discriminates regions with preserved viability from those with relevant myocardial damage.