Ventilator management decisions in acute lung injury could be better informed with knowledge of the patient's transpulmonary pressure, which can be estimated using measurements of esophageal pressure. Esophageal manometry is seldom used for this, however, in part because of a presumed postural artifact in the supine position. Here, we characterize the magnitude and variability of postural effects on esophageal pressure in healthy subjects to better assess its significance in patients with acute lung injury. We measured the posture-related changes in relaxation volume (V_rel) and total lung capacity (TLC) in 10 healthy subjects in 4 postures: upright, supine, prone, and left lateral decubitus. Then, in the same subjects, we measured static pressure-volume characteristics of the lung over a wide range of lung volume in each posture using an esophageal balloon-catheter. Transpulmonary pressure during relaxation (P_L,rel) averaged 3.7 ± 2.0 cm H₂O upright and -3.3 ± 3.2 cm H₂O supine. Approximately 58% of the decrease in P_L,rel between the upright and supine postures was due to a corresponding decrease in V_rel. The remaining 2.9 cm H₂O difference is consistent with reported values of a presumed postural artifact. Relaxation volumes and pressures in prone and lateral postures were intermediate. To correct estimated transpulmonary pressure for the effect of lying supine, we suggest adding 3 cm H₂O (95% C.I. -1 to +7 cm H₂O). We conclude that postural differences in estimated transpulmonary pressure at a given lung volume are small when compared with the substantial range of P_L,rel in patients with acute lung injury.