OBJECTIVE To assess the influence of myocardial structure and pericardial constraint during exercise ischemia on regional left ventricular passive elastic properties. METHODS Left ventricular regional function was assessed at rest and during exercise using biplane angiography and high-fidelity pressure measurements. Twenty patients with either normal (n = 7) or stenotic coronary arteries (n = 13) were studied before and after successful bypass surgery. At the time of surgery, left ventricular transmural biopsies were taken from a normally perfused and a hypoperfused left ventricular region. RESULTS Regional stiffness increased in the ischemic zone during exercise, but remained unchanged after revascularization. Regional fibrosis was significantly enhanced in the ischemic region compared with that in the normally perfused zone. No correlation was found between structural data and regional passive elastic properties, but there was a significant correlation between right atrial pressure and the asymptote of the diastolic pressure--volume relationship. CONCLUSIONS Acute regional diastolic dysfunction can be observed during exercise in patients with coronary artery disease. Structural changes seem to have a minor role in the occurrence of diastolic dysfunction in the absence of myocardial infarction. The observed upward shift of the pressure-volume relationship during ischemia can be attributed to pericardial constraint that is manifested by an increase in right arterial pressure.