During atrioventricular (AV) sequential pacing from the right heart, the interval between the left atrium and ventricle may vary from the programmed AV interval depending on the position of the atrial and ventricular electrodes and interatrial and interventricular conduction. The aim of this study was to determine the hemodynamic effects of altering the left AV interval while keeping the programmed AV interval constant. Four male and 17 female patients, aged 49 +/- 15 years were studied. The left AV interval was measured by a catheter in the coronary sinus. Stroke volume and mitral flow were measured by simultaneous echo Doppler during AV sequential pacing from the right atrial appendage and right ventricular apex at programmed AV intervals of 100, 60, and 6 ms. The atrial catheter was then positioned on the atrial septum and the measurements repeated. With the atrial catheter in the right atrial appendage, interatrial activation time (118 +/- 20 ms) was similar to interventricular activation time (125 +/- 21 ms) and the left AV interval was almost identical to the programmed right AV interval. There was a significant correlation between interatrial and interventricular activation times (r = 0.8; P < 0.001). Positioning the atrial electrode on the septum decreased interatrial activation time by 39 +/- 12 ms and increased the left AV interval by a similar amount. At a programmed AV interval of 60 ms, the left AV interval increased from 67 +/- 15 ms to 105 +/- 17 ms after the atrial catheter was repositioned from the appendage to the septum (P < 0.001). Compared to pacing from the right atrial appendage, atrial septal pacing increased mitral A wave velocity integral (2.8 +/- 1.4 vs 4.4 +/- 1.7 cm at a programmed AV interval of 60 ms, P < 0.01), decreased E wave velocity integral (8.1 +/- 2.2 vs 6.1 +/- 2.4 cm, P < 0.001) but did not alter stroke volume (44.8 +/- 10.6 vs 44.9 +/- 10.1 mL). In contrast, a 40 ms decrease in the programmed right AV interval from 100 to 60 ms decreased stroke volume from 48.0 +/- 10.0 to 44.9 +/- 10.2 mL (P < 0.001). There was a strong relationship between interatrial and interventricular conduction so that patients with prolonged interatrial conduction still had equivalent left and right AV intervals during atrioventricular sequential pacing from the right atrial appendage and right ventricular apex. Positioning the atrial electrode on the septum decreases interatrial activation time and increases the left AV interval by about 40 ms but has minimal hemodynamic effect in patients without heart failure.