This study sought to characterize mechanical activation in pulmonary arterial hypertension (PAH) using 2-dimensional echocardiography with tissue Doppler imaging. Whether pathologic alterations of the right ventricle in PAH affect interventricular dyssynchrony due to changes in mechanical activation of the septum and the right ventricle is unclear. We studied 20 patients with PAH (14 women, mean age 55 +/- 16 years) and 20 healthy controls (15 women, mean age 41 +/- 11 years) that underwent tissue Doppler imaging between July 2006 and May 2007. PAH was associated with accelerated right ventricular (RV) (p <0.0001) and septal (p = 0.022) activation times, but no differences were found in lateral wall activation times between groups (p = 0.35). Measures of ventricular dyssynchrony indicated that patients with PAH had significantly lower RV-lateral wall delays (patients 3.2 +/- 66.2 ms vs controls 56.7 +/- 52.0 ms, p = 0.007), reflecting a faster activation of the right ventricle relative to the lateral wall than controls. In conclusion, PAH is associated with interventricular dyssynchrony manifested by accelerated RV free wall and septal activation times. Whether such dyssynchrony should serve as a therapeutic target remains to be determined.