The alterations in regional diastolic mechanics that occur during regional myocardial ischemia (creep and increased myocardial stiffness) may be the result of interactions between the ischemic and surrounding nonischemic myocardium rather than the direct result of ischemia. Thus similar changes may not occur when the entire left ventricle is ischemic. To investigate this proposition, left ventricular diastolic mechanics were studied in 7 chronically instrumented conscious dogs during global left ventricular ischemia. The anterior-posterior, septal-free wall, and base-apex axes of the left ventricle were measured with ultrasonic dimension transducers. Left and right ventricular pressures were measured with micromanometers. Myocardial blood flows were measured with left atrial injections of 15 μm radioactive microspheres. Global left ventricular ischemia was induced by hydraulic constriction of the left main coronary artery, which resulted in a 54% decrease in mean left ventricular subendocardial blood flow. Left ventricular volume, midwall circumference, and midwall circumferential stress were calculated from ellipsoidal shell theory. To construct pressure-strain and stress-strain relationships from diastolic data collected during vena caval occlusions, all measured and calculated dimensions were normalized to Lagrangian strains (fractional extension from unstressed dimension). During ischemia, creep (elongation of unstressed dimension) occurred in each of the three left ventricular axes. The mean unstressed dimension of the anterior-posterior axis increased from 5.39 ± 0.53 to 5.85 ± 0.50 cm (p ≤ .05); the septal-free wall unstressed dimension increased from 5.11 ± 0.53 to 5.72 ± 0.80 cm (p ≤ .05); and the base-apex unstressed dimension increased from 7.04 ± 0.61 to 7.25 ± 0.65 cm (p ≤ .05). The relationship between diastolic midwall circumferential stress and strain shifted upward and to the left with ischemia, indicating that an increase in intrinsic myocardial stiffness had occurred. As a result of these mechanical alterations, there was a decrease in left ventricular chamber compliance that was manifested by a leftward shift of the diastolic pressure-volume strain relationship. Neither systolic bulging nor dysynchronous systolic shortening occurred in any of the three left ventricular spatial axes during ischemia. Thus, during global left ventricular ischemia, changes in diastolic mechanics identical to those that occur during regional ischemia account for a loss of left ventricular chamber compliance. This suggests that although systolic dyskinesia during regional ischemia may result from interactions between areas of ischemic and nonischemic myocardium, changes in regional diastolic mechanics are the direct result of ischemia.