The optimal method for estimating transpulmonary pressure (i.e. the fraction of the airway pressure transmitted to the lung) has not yet been established. In this study on 44 patients with acute respiratory distress syndrome (ARDS), we computed the end-inspiratory transpulmonary pressure as the change in airway and esophageal pressure from end-inspiration to atmospheric pressure (i.e. release derived) and as the product of the end-inspiratory airway pressure and the ratio of lung to respiratory system elastance (i.e. elastance derived). The end-expiratory transpulmonary pressure was estimated as the product of positive end-expiratory pressure (PEEP) minus the direct measurement of esophageal pressure and by the release method. The mean elastance- and release-derived transpulmonary pressure were 14.4 +/- A 3.7 and 14.4 +/- A 3.8 cmH(2)O at 5 cmH(2)O of PEEP and 21.8 +/- A 5.1 and 21.8 +/- A 4.9 cmH(2)O at 15 cmH(2)O of PEEP, respectively (P = 0.32, P = 0.98, respectively), indicating that these parameters were significantly related (r (2) = 0.98, P < 0.001 at 5 cmH(2)O of PEEP; r (2) = 0.93, P < 0.001 at 15 cmH(2)O of PEEP). The percentage error was 5.6 and 12.0 %, respectively. The mean directly measured and release-derived transpulmonary pressure were -8.0 +/- A 3.8 and 3.9 +/- A 0.9 cmH(2)O at 5 cmH(2)O of PEEP and -1.2 +/- A 3.2 and 10.6 +/- A 2.2 cmH(2)O at 15 cmH(2)O of PEEP, respectively, indicating that these parameters were not related (r (2) = 0.07, P = 0.08 at 5 cmH(2)O of PEEP; r (2) = 0.10, P = 0.53 at 15 cmH(2)O of PEEP). Based on our observations, elastance-derived transpulmonary pressure can be considered to be an adequate surrogate of the release-derived transpulmonary pressure, while the release-derived and directly measured end-expiratory transpulmonary pressure are not related.