Some patients with ventricular tachycardia (VT) remain virtually asymptomatic, whereas others have syncope despite similar VT rates. The role of ventricular activation site on left ventricular (LV) function was examined in 10 patients undergoing electrophysiologic evaluation for recurrent ventricular arrhythmias. Radionuclide ventriculograms were acquired to calculate LV volumes and aortic or LV pressure was measured during right atrial and right ventricular (RV) pacing. RV apical pacing resulted in end-diastolic volumes similar to those achieved with right atrial pacing (171 +/- 27 vs 175 +/- 19 ml), whereas RV outflow tract pacing showed a trend toward lower volumes (168 +/- 32 vs 177 +/- 33 ml). Comparison between RV apical and RV outflow tract pacing showed that apical activation resulted in higher end-diastolic volumes (216 +/- 26 vs 194 +/- 22 ml, p = 0.020), end-systolic volumes (175 +/- 25 vs 158 +/- 20 ml, p = 0.041), stroke volumes (42 +/- 4 vs 36 +/- 6 ml, p = 0.046), peak rates of LV ejection (309 +/- 57 vs 245 +/- 40 ml/s, p = 0.034) and peak rates normalized for differences in end-diastolic volume (1.5 +/- 0.3 vs 1.3 +/- 0.3; p = 0.047) without a significant increase in peak pressures (131 +/- 12 vs 127 +/- 14 mm Hg, p greater than 0.30) or ejection fractions (24 +/- 5 vs 22 +/- 4%, p = 0.187). These changes were accompanied by an increase in LV/RV stroke count ratios during RV apical vs RV outflow tract pacing (1.6 +/- 0.2 vs 1.2 +/- 0.2, p = 0.030), suggesting the development of mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)