In this study we introduce a new concept of systolic myocardial stiffness that extends the Suga-Sagawa maximum ventricular elastance concept to the myocardium. End-systole is defined as the time of maximum systolic myocardial stiffness (max Eav), which we examined for its load independence and sensitivity to changes in the inotropic state and to heart rate. Seven adult mongrel dogs were instrumented with ultrasonic crystals for measurements of long and short axes and left ventricular wall thickness, and a high-fidelity micromanometer was inserted for measurement of left ventricular pressures. Preload and afterload were altered by inferior vena cava occlusion, nitroprusside, angiotensin II, atropine, propranolol, and various combinations with propranolol. End-systolic stressstrain relations (slope: max Eav) were linear in all seven dogs, implying that end-systolic myocardial stiffness is independent of end-systolic stress. Changes in max Eav (for constant preload and afterload) reflected changes in the ejection fraction; max Eav was also insensitive to propranolol and to changes in heart rate over the range from 120 to 180 beats/min. End-systolic pressure-volume relations (ESPVRs), derived analytically from these stress-strain relations, were nonlinear, and estimates of volume at zero stress (Vom) were always positive. On the other hand, ESPVRs obtained on the basis of the Suga-Sagawa maximum ventricular elastance concept, were linear, and volume at zero pressure (VOP) estimated by linear extrapolation was negative in one case. Based on the concept of systolic myocardial stiffness, the slope of the ESPVR varies with end-systolic volume and attains its maximum value (Emax) at zero end-systolic pressure. Normalization of Emax with Vom demonstrated a close relationship to max Eav. Thus both max Eav and Vom and Emax are ideal variables for assessing changes in myocardial contractility when preload and afterload are constant. Furthermore, Vom and max Eav permit development of the entire ejection fraction-afterload relationship for a given preload, thus providing a method for comparing myocardial contractile states between ventricles. Circulation 76, No. 2, 343–356, 1987.