Hypoxic pulmonary disorders and head injuries associated with increased intracranial pressure (ICP) frequently co-exist. Positive end-expiratory pressure (PEEP) improves hypoxemia but has been reported to impede cerebral venous return, potentially causing a further increase in ICP. This study examined the effects of PEEP on ICP at different levels of brain compliance. continuous ICP recordings were obtained after insertion of Scott cannulas to the lateral ventricles of seven comatose patients. Brain compliance was assessed by calculation of the pressure volume index. Patients were maintained in a 30 degrees head-up position. Maintenance of PEEP to levels of 40 cm H2O pressure for as long as 18 hours did not increase ICP in patients with either normal or low intracranial compliance, and did not increase ICP in the absence of pulmonary disease. Central venous pressure and pulmonary artery wedge pressure increased proportionately as PEEP was increased. No consistent changes were found in blood pressure recordings, nor were there any reductions in cardiac output found during the studies. Abrupt discontinuation of PEEP did not result in increased ICP except for a transient rise on two occasions when respiratory secretions became copious and the patients were inadequately ventilated. Improved oxygenation in two patients as a result of PEEP was concomitant with improved intracranial compliance and neurological status. In patients with brain injuries, PEEP improves arterial oxygenation without increasing ICP as previously supposed. Consequently, PEEP is a valuable form of therapy for the comatose patient with pulmonary disorders such as pneumonia or pulmonary edema.