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We discuss a case of severe pneumonia with pneumatoceles in a 2-month old infant. Despite peak and plateau airway pressures kept below 30 and 25 cmH(2)O, respectively, the infant developed bilateral pneumothorax and pneumomediastinum caused by pneumatocele rupture, necessitating bilateral intercostal drainage. Application of positive end-expiratory pressure (PEEP) of 10 cmH(2)O at FIO(2) of 0.7 worsened oxygenation, and transthoracic echocardiography showed right-to-left shunting of blood through the patent foramen ovale. Therefore, PEEP had to be tapered to 6 cmH(2)O, and ventilation carried out at FIO(2) of 1 until the lung condition improved. The open lung strategy of higher increments of PEEP and lower FIO(2) for lung protective ventilation actually proved deleterious to our patient. We conclude that a subset of patients with acute respiratory distress syndrome with refractory hypoxaemia may have right-to-left shunting of blood through a patent foramen ovale. This can be detected by echocardiography, and these patients may benefit from a ventilation strategy aimed at lowering pulmonary vascular resistance.