BACKGROUND Platypnea and Orthodeoxia have been described with congenital heart and severe lung diseases. METHODS We report 4 patients in whom platypnea and orthodeoxia developed after pneumonectomy. In these patients the mean oxygen saturation on room air was 65% (range, 45% to 79%) in the supine position. On O2 therapy it improved to 94% (range, 80% to 99%). When the patients assumed the erect position and were receiving O2 therapy the saturation dropped to a mean of 76% (range, 56% to 82%) and the patients complained of shortness of breath. Cardiac catheterization revealed a mean pulmonary capillary wedge pressure of 11.6 mm Hg (range, 7 to 18 mm Hg). All patients had normal right atrial pressure. A right-to-left interatrial shunt through a patent foramen ovale was documented by transesophageal echocardiography and dynamic ultrafast magnetic resonance imaging. The patients underwent surgical closure of the patent foramen ovale. RESULTS In the erect position, the room air O2 saturation improved to a mean of 95% (range, 92% to 99%), and the shortness of breath disappeared. CONCLUSIONS Postpneumonectomy patients complaining of shortness of breath should be assessed for platypnea and orthodeoxia. A right-to-left interatrial shunt through a patent foramen ovale can occur even in the absence of elevated right heart pressures, especially after right pneumonectomy, and is accentuated in the upright posture. Surgical correction of the patent foramen ovale can produce dramatic improvement.