Background: In ventilated patients, PEEP can be applied to establish a positive transpulmonary pressure (airway minus pleural pressure, Ptp) with the goal of maintaining open lungs. However, Ptp is usually determined while supine and patients are often rotated to other positions. To assess positional affects, we studied Ptp and lung volume status (functional residual capacity or FRC) in swine placed in different positions. Methods: Twelve anesthetized swine (30-35 kg) were prepared for the protocol by esophageal balloon-catheter placement, tracheotomy to facilitate mechanical ventilation and chest tube placement to instill liquid and create a pleural effusion (compressive lung stress). Ventilation was kept constant throughout the study at VT = 10 ml/kg, f=15, I:E=1:2 with PEEP set at 1 and 10 cmH2O (Carestation, GE Healthcare, Madison, WS). Monitoring included Ptp and FRC as unilateral pleural effusion was induced and PEEP of 1 and 10 cmH2O were applied in 5 positions: supine, prone, right lateral, left lateral and fowler’s. Results: FRC was increased by PEEP = 10 cmH2O in all positions, as expected (figure). The fowler’s position had significantly greater FRC than other tested positions. Mean end-expiratory Ptp in the supine position displayed greater compressive stress (-6.8 cmH2O) than the fowler’s (vs. -3.7, p<.001) or right lateral (vs. -5.1, p=.04) positions. In swine not pre-treated with a fluid bolus, hypotensive episodes were encountered when transferring to the fowler’s position. Conclusions: Fowler’s position can be recommended to increase lung volume and reduce compressive lung stress, however, blood pressure must be monitored when changing to fowler’s. Esophageal pressure may not represent the most vulnerable lung in positions other than supine. Esophageal balloon height may explain the measured between-position differences in Ptp. Support provided by HPRF and GE Healthcare.