The goal of this work was to investigate the hemodynamic effects of simultaneous left ventricular (LV) pacing site (LVPS) and interventricular pacing delay (VVD) variation with biventricular pacing (BiVP) during acute LV failure. Simultaneously varying LVPS and VVD with BiVP has been shown to improve hemodynamics during acute right ventricular (RV) failure. However, effects during acute LV failure have not been reported. In six open-chest pigs, acute LV volume overload was induced by regurgitant flow via an aortic-LV conduit. Epicardial BiVP was implemented with right atrial and ventricular leads and a custom LV pacing array. Fifty-four LVPS-VVD combinations were tested in random order. Cardiac output was evaluated by aortic flow probe, ventricular systolic function by maximum rate of ventricular pressure change, and mechanical interventricular synchrony by normalized RV-LV pressure diagram area. Simultaneous LVPS-VVD variation improved all measures of cardiac function. The observed effect was different for each functional index, with evidence of LVPS-VVD interaction. Compared with effects of LVPS-VVD variation in a model of acute RV failure, hemodynamic changes were markedly different. However, in both models, maximum rate of ventricular pressure change of the failing ventricle was improved with synchronous interventricular contraction, suggesting that, in acute ventricular failure, BiVP can recruit the unstressed ventricle to support systolic function of the failing one. Thus simultaneously varying LVPS and VVD with BiVP during acute ventricular failure can improve cardiac function by "interventricular assist", with hemodynamic effects dependent on the type of failure. This supports the potential utility of temporary BiVP for the treatment of acute ventricular failure commonly seen after cardiac surgery. Copyright © 2009 the American Physiological Society.