Controversy exists as to whether short AV delay pacing is beneficial in left ventricular dysfunction with the studies performed coming to disparate conclusions. The right ventricular apical pacing previously studied results in asynchronous contraction and relaxation sequences and may limit the potential benefits of short AV delay pacing. In this study the hemodynamic effects of septal (resulting in a more physiological activation sequence) and apical right ventricular activation were compared in 15 patients with heart failure. VDD pacing with AV delays of 50, 100, and 150 msec was evaluated. Apical VDD pacing did not increase the cardiac output significantly, 4.1 +/- 0.75 to 4.45 +/- 0.74 L/min, whereas septal VDD pacing increased the cardiac output to 4.86 +/- 0.79 L/min (P = 0.037). Apical pacing increased the cardiac output in 10 patients and septal pacing in 11 patients. We conclude that selected patients with ventricular dysfunction benefit from short AV delay pacing. Septal ventricular activation confers significant hemodynamic improvements over apical activation.