There is some controversy regarding the mechanisms of an upward shift in the left ventricular diastolic pressure-volume curve during ischemia. The effects of handgrip exercise on the pressure-volume curve were examined in 21 patients with coronary artery disease and in 6 control subjects. Pressure-volume curves were constructed from digitized left ventricular pressure and volume derived from biplane left ventriculogram. Diastolic pressure-volume curve shifted upward in 12 patients with coronary artery disease during handgrip exercise (Group 1), but not in the other 9 patients who were similarly afflicted (Group 2). The upward shift did not occur in any control subject. No difference was observed in rate-pressure product gain during exercise. In Group 1, left ventricular end-diastolic pressure increased (p less than 0.01) and ejection fraction was reduced (p less than 0.01), although it did not change in Group 2. In Group 1, the time constant was prolonged (p less than 0.01) with no change in the coefficient for elastic modulus. In Group 2, these parameters remained unchanged. Group 1 was accompanied by more extensive asynergy than Group 2. Thus, isometric handgrip exercise resulted in an upward shift in the diastolic pressure-volume curve in patients with coronary artery disease. Incomplete relaxation and/or the viscoelastic properties of the left ventricle associated with ischemia could be responsible for this phenomenon.