In the excised canine left ventricle, the end-systolic pressure-volume relationship (ESPVR) has been shown to be approximately linear over the working range of loading conditions when coronary arterial pressure (CAP) is maintained constant, independent of loading conditions. To investigate the ESPVR under the more intact physiological condition in which the CAP varies with loading on the left ventricle, we studied the effect of changes in CAP on the ESPVR in 10 excised cross-circulated canine ventricles which were contracting isovolumically. The ESPVR, determined from isovolumic contractions at four different volumes, was reasonably independent of CAP as long as CAP remained above a critical pressure (67.0 +/- 22.1 mm Hg). Below this pressure, the slope of ESPVR decreased although the volume axis intercept (V0) remained unaltered. These findings indicate that under physiological conditions, where there is a close coupling of CAP to systolic left ventricular pressure, the ESPVR should become nonlinear in the low preload or afterload regions. When CAP was varied with the left ventricular pressure in five ventricles, the ESPVR indeed became nonlinear in the low-load region. We conclude that the ESPVR in intact conditions is reasonably linear in the physiological load range, but it can be nonlinear in the low-load range.