We hypothesized that pacing, which provided a rapid uniform contraction of the ventricles with a narrower QRS, would produce a better stroke volume and cardiac output (CO). We sought to study whether pacing simultaneously at two sites in the right ventricle (right ventricular apex and outflow tract) would provide a narrower QRS and improved CO in 11 patients undergoing elective electrophysiology studies. Patients were studied by transthoracic echocardiography measurement of CO using the Doppler flow velocity method in normal sinus rhythm, AOO pacing (rate 80), DOO pacing in the right ventricular apex (AV delay 100 ms), DOO pacing in the right ventricular outflow tract, and DOO pacing at both right ventricular sites simultaneously in random order. The COs were 5.42 +/- 1.83, 5.61 +/- 1.97, 5.67 +/- 1.6, 5.84 +/- 1.68, and 5.86 +/- 1.52 L/min, respectively (no significant difference by repeated measures analysis of variance [ANOVA]). The QRS durations were 0.09 +/- 0.02, 0.09 +/- 0.02, 0.13 +/- 0.027, 0.13 +/- 0.03, and 0.11 +/- 0.03 secs respectively. Repeated measures ANOVA showed that the QRS duration significantly increased with right ventricular apex or right ventricular outflow tract pacing compared to sinus rhythm and AOO pacing (P < 0.001) but then diminished with pacing at both sites (P < 0.01). QRS duration was not correlated with CO, however the change in QRS duration correlated significantly with the change in CO when pacing was performed at the two right ventricular sites simultaneously. In conclusion, during DOO pacing, there was a trend for pacing in the right ventricular outflow tract or both sites to improve the CO compared to the right ventricular apex. With simultaneous pacing at both ventricular sites, the QRS narrowed. Further studies will be required to see if this approach has value in patients with poor left ventricular function or congestive heart failure.