Experimental animal data have indicated that the site of ventricular tachycardia origin and, hence, the degree of asynchronous contraction, may influence the hemodynamic tolerance during sustained ventricular tachycardia. However, data in man are scarce. We studied patients with preserved left ventricular function and absence of significant coronary artery disease. Ventricular tachycardia was simulated with rapid pacing (at 120 and 150 beats/min), performed randomly, from the right ventricular apex or the right ventricular outflow tract. Following pacing from one site, it was repeated from the alternate site. Compared to outflow tract pacing, QRS duration was significantly longer during rapid pacing from the apex. Left ventricular pressure was recorded using a micromanometer-tipped catheter. During sinus rhythm, peak systolic pressure was 142 +/- 14 mmHg; at 120 beats/min, it decreased to 109 +/- 12 mmHg during pacing from the apex and to 127 +/- 21 mmHg during pacing from the outflow tract (P = 0.008). This difference diminished at 150 beats/min (101 +/- 16 mmHg vs 112 +/- 16 mmHg, respectively, P = 0.21). During sinus rhythm end-diastolic pressure was 13 +/- 1 mmHg, which did not change significantly during pacing at 120 beats/min. During pacing at 150 beats/min, end-diastolic pressure increased to 21 +/- 3 mmHg during pacing from the apex and to 16 +/- 2 mmHg during pacing from the outflow tract (P = 0.005). Changes in first derivative of pressure and in isovolumic relaxation time constant were comparable during pacing from the two sites. Thus, it seems that tachycardias originating from the right ventricular outflow tract result in more favorable left ventricular hemodynamics, compared to those from the right ventricular apex.