What is the central question of this study? Right ventricular dyssynchrony in severe pulmonary hypertension is associated with a poor prognosis. However, it has recently been observed in patients with lung or connective tissue disease and pulmonary artery pressure at the upper limits of normal. The mechanisms of right ventricular dyssynchrony in pulmonary hypertension remain uncertain. What is the main finding and its importance? Acute hypoxic breathing, but not normoxic exercise, induces an increase in right ventricular dyssynchrony detected by speckle tracking echocardiography in healthy subjects. These results add new insights into the determinants of right ventricular dyssynchrony, suggesting a role for systemic factors added to afterload in the pathophysiology of right ventricular inhomogeneity of contraction. ⋯ Pulmonary hypertension (PH) has been shown to be associated with regional inhomogeneity (or dyssynchrony) of right ventricular (RV) contraction. Right ventricular dyssynchrony is an independent predictor of decreased survival in advanced PH, but has also been reported in patients with only mildly elevated pulmonary artery pressure (PAP). The mechanisms of RV dyssynchrony in PH remain uncertain. Our aim was to evaluate RV regional function in healthy subjects during acute hypoxia and during exercise. Seventeen healthy subjects (24 ± 6 years) underwent a speckle tracking echocardiography of the RV at rest in normoxia and every 15 min during a 60 min exposure to hypoxic breathing ( FIO2 12%). Ten of the subjects also underwent an incremental cycle ergometry in normoxia to 100 W, with the same echocardiographic measurements. Dyssynchrony was measured as the SD of the times to peak systolic strain of the four basal and mid RV segments corrected for the heart rate (RV-SD4). RV-SD4 increased during hypoxia from 12 ± 7 to 22 ± 11 ms in spite of mild increases in mean PAP (mPAP) from 15 ± 2 to 20 ± 2 mmHg and pulmonary vascular resistance (PVR) from 1.18 ± 0.15 to 1.4 ± 0.15 Wood units (WU). During exercise RV-SD4 did not significantly change (from 12 ± 6 ms to 14 ± 6 ms), while mPAP increased to 25 ± 2 mmHg and PVR was unchanged. These data show that in healthy subjects, RV contraction is inhomogeneous in hypoxia but not during exercise. Since PAP increases more during exercise, RV dyssynchrony in hypoxia may be explained by a combination of mechanical (RV afterload) and systemic (hypoxia) factors.