Respiratory system mechanics were evaluated in a 22-year-old asymptomatic man with absence of the left hemidiaphragm. We described changes in esophageal pressure (Pes), gastric pressure (Pga), chest wall configuration, and mediastinal motion during tidal breathing, breaths to total lung capacity (TLC), and Mueller maneuvers in the upright and supine position. We predicted that contraction of the single hemidiaphragm would drive the abdominal contents caudal on the side with the intact hemidiaphragm and displace the abdominal contents cephalad on the other side. This would drive the mediastinum toward the side with the intact diaphragm, thereby reducing its effectiveness in expanding the lung on that side. When upright, this effect would be minimized to the extent that the rib cage muscles lower pleural pressure in the thorax without the diaphragm. We found that (vital capacity) VC and TLC were greater upright than supine and that Pga deflections were almost as strongly negative as Pes deflections during upright quiet breathing and breaths to TLC. Thus the rib cage muscles enhanced the inspiratory action of the right hemidiaphragm in the upright position. In the supine position, Pes became negative without change of Pga during breaths to TLC and quiet inspirations. Here, contraction of the hemidiaphragm was the dominant mechanism generating the inspiratory pressure. During maximal Mueller efforts, the mediastinum shifted toward the side with the intact diaphragm in both positions and the maximum inspiratory pressures were low. These pressures were likely to have been limited by both the finite impedance to rotation of the thoracoabdominal contents or mediastinum and a mechanical disadvantage of the remaining hemidiaphragm. We conclude that the effectiveness of the single hemidiaphragm as an inspiratory pump requires passive impedance of the abdominal viscera and mediastinum and is enhanced in the upright position by the action of the rib cage muscles.