Intermittent hypoxia due to sleep apnea syndrome is associated with cardiovascular diseases. However, the precise mechanisms by which intermittent hypoxic stress accelerates cardiovascular diseases are largely unclear. The aim of this study was to investigate the role of gp91phox-containing NADPH oxidase in the development of left ventricular (LV) remodeling induced by intermittent hypoxic stress in mice. Male gp91phox-deficient (gp91^-/-) mice (n=26) and wild-type mice (n=39) at 7 to 12 weeks of age were kept under intermittent hypoxia (30 seconds of 4.5-5.5% oxygen followed by 30 seconds of 21% oxygen level for 8 hours per day during daytime) or normoxia for 10 days. Mean blood pressure and LV systolic and diastolic function were not changed by intermittent hypoxia in either wild-type or gp91^-/- mice, although right ventricular systolic pressure tended to be increased. In wild-type mice, intermittent hypoxic stress significantly increased the diameter of cardiomyocytes and interstitial fibrosis in LV myocardium. Furthermore, intermittent hypoxic stress increased superoxide production, 4-hydroxy-2-nonenal protein, TNF- and transforming growth factor (TGF)- mRNA, and NF-B binding activity in wild-type mice, but not in gp91^-/- mice. These results suggest that gp91 phox-containing NADPH oxidase plays a crucial role in the pathophysiology of intermittent hypoxia-induced LV remodeling through an increase of oxidative stress.