A comprehensive study on open chest anesthetized dogs was done to investigate the influence of intraventricular activation order on cardiac performance and to evaluate the degree to which entry into the conduction system might contribute to the synchrony of contraction in the ventricle opposite the stimulus site. Intraventricular pressures were measured during premature beats from several ventricular sites and over the entire range of the cardiac cycle. For each site, intraventricular pressures during the premature beats were plotted vs. time of delivery of the stimulus and also vs. time of onset of pressure rise in the ventricle being considered. The prior observation that higher ventricular pressures occur during premature beats initiated in the opposite ventricle was confirmed. Evidence is presented that the major factor responsible is the increased filling and recovery interval permitted by the conduction time of the activation front arriving from the opposite ventricle. After correction for filling and recovery time, there were still differences due to site of origin of the premature beat, with those delivered to the apex resulting in the highest left ventricular pressures. The hypothesis that a more synchronous contraction results from stimulation of sites on the contralateral, rather than the ipsilateral ventricle, was not substantiated. While there is lack of agreement that cardiac performance is significantly altered by stimulus site during ventricular pacing at a fixed rate, there is general agreement that variations in performance related to stimulus site do occur with ventricular premature beats. During premature ventricular beats, marked and systematic differences in the intraventricular pressure in the stimulated and contralateral ventricle have been noted, with the directly stimulated ventricle attaining a smaller fraction of the systolic pressure in that ventricle during the preceding normally conducted beat.4 ' 6 Wiggers noted this difference and suggested that the excitation pattern is more