In isolated isovolumic ventricles and in in situ ventricles under nonsteady-state conditions, alterations in load have been shown to affect electrophysiological properties via contraction-excitation feedback. However, the effect of alterations in loading conditions on electrophysiological properties in normal ventricles under physiological loading conditions remains unknown. Furthermore, the arrhythmogenic significance of these load-induced electrophysiological changes is uncertain. We increased end-diastolic volume (27 +/- 4 ml vs. 51 +/- 6 ml) and assessed conduction, refractoriness, ventricular fibrillation thresholds (VFTs), and inducibility of ventricular arrhythmias in 14 isolated blood-perfused ejecting canine ventricles under steady-state conditions. We also examined the effect of increased end-diastolic volume on refractoriness and monophasic action potential (MAP) duration and contour under isovolumic versus ejecting conditions. Under ejecting conditions, increased end-diastolic volume resulted in very small (less than 1.5%) changes in the absolute refractory period (10 mA) and in local activation time but no change in local electrogram duration, overall dispersion of refractoriness, MAP duration or contour, VFT, or inducibility of ventricular arrhythmias. Increased volume loading under isovolumic conditions resulted in a very slight (less than 1%) shortening of MAP duration and refractoriness but had no effect on the MAP contour. These findings provide strong evidence that alterations in volume load are of little electrophysiological or arrhythmogenic importance in normal canine ventricles under physiologically loaded conditions (contraction-excitation feedback, load and arrhythmias, volume load).