The present case describes an acute respiratory-related hemodynamic failure during a single left lung transplantation in a 32-year-old woman suffering from end-stage pulmonary lymphangiomyomatosis. During the first 5 min of single right lung ventilation, a progressive increase in airway pressure and decrease in tidal volume associated with a decrease in arterial pressure and Spo2 occurred that were successfully countered by reventilation of the left lung. Proper positioning of the double-lumen tube was confirmed with a fiberoptic bronchoscope. Despite deliberate hypoventilation, within a few respiratory cycles, each further attempt at single lung ventilation was followed by abrupt hypotension, increase in pulmonary artery pressure, while airway pressure rose and tidal volume collapsed. The surgical team saw no signs of right pneumothorax. In these circumstances, cardiopulmonary bypass was required to perform pneumonectomy and grafting. Postoperatively a right anterior pneumothorax remained undiscovered on standard radiograph but was later revealed on soft radiograph. This acute intraoperative respiratory failure could equally well have been related to air trapping, in which case, however, deliberate hypoventilation would have been effective. In addition, the striking difference between the progressive onset of the first episode of hemodynamic failure and the immediate onset of the others argues in favor of a pneumothorax being at cause. Patients with pulmonary lymphangiomyomatosis are at high risk for intraoperative pneumothorax, but in our case, it could not be confirmed and treated during the surgical procedure without putting the patient at high risk for lung injury because of pleurodesis due to earlier pleural abrasion. This case again clearly shows the need to have cardiopulmonary bypass whenever single lung transplantation is performed.