Physiological loads were imposed on contracting isolated cat papillary muscles. The interaction of a hypothetical cylindrical ventricle with a three-element vascular impedance model dictated these physiological loads. The length-tension relation of the physiologically loaded muscle and the pressure-volume relation of the hypothetical ventricle were simultaneously analyzed while the resistive and capacitive components of the vascular impedance were varied widely. Both the end-systolic muscle length-tension relation and the end-systolic ventricular pressure-volume relation were constructed using stepwise increments in either peripheral vascular capacitance or peripheral vascular resistance. The slope of the relation line connecting the end-systolic pressure-volume points under stepwise increases in resistive load was smaller (p< 0.0005) than the slope of this line under stepwise increases in capacitive load. Therefore, the end-systolic pressure-volume relation behaves differently with respect to capacitive and resistive loads. The different loading pattern within the same beat under these varying loading conditions and the coincidence of end-systole with end-ejection in these naturally ejecting contractions are responsible for the shifts in slope of the end-systolic pressure-volume relation. Neither the slope nor the volume intercept of the end-systolic pressure-volume relation was changed when initial muscle length was decreased from 1.0 to 0.95 ImaxWhen the Ca2+concentration in the bathing solution was increased from 2.5 to 7.5 mM, the slope of the end-systolic pressure-volume relation increased (P< 0.0005), and the volume intercept of the curve decreased (P< 0.025). These results are similar to data reported for conscious animals and to data obtained from catheterization of the human left ventricle.Circ Res 46: 20-26, 1980