A 62-year-old woman was referred for evaluation of hypoxemia. Despite a resting SaO(2) of 89%, she was otherwise asymptomatic. The arterial blood gas on room air demonstrated a pO(2) of 58 mm Hg. Two shunt studies confirmed a shunt fraction of 25%. Echocardiogram with agitated saline demonstrated bubbles in the left atrium. Nuclear perfusion study revealed no uptake over the kidneys or brain. Computed tomography of the chest and cardiac magnetic resonance imaging confirmed the presence of a large shunt (azygous continuation of the inferior vena cava [ACIVC] with anomalous hepatic vein drainage). A large shunt fraction dictates either significant cardiac septal defect or an extracardiac shunt. The finding of ACIVC should prompt consideration of other vascular or cardiac abnormalities. The true incidence of isolated ACIVC is not known, as limited ACIVC may remain asymptomatic. However, the spectrum of vascular, cardiac and somatic abnormalities that may accompany ACIVC is quite varied.