We investigated whether end-expiratory lung volume (EELV) or lung mechanical parameters are more sensitive for the detection of a compromised gas exchange during bronchoconstriction and after surfactant depletion. EELV was determined via SF(6) multiple breath wash-outs in mechanically ventilated rabbits while a positive end-expiratory pressure (PEEP) of 1, 3 or 7 cm H(2)O was maintained. Airway resistance (R(aw)) and parenchymal elastance (H) were estimated from the pulmonary input impedance measured at each PEEP level by means of forced oscillations. Measurements were repeated during i.v. methacholine (MCh) infusions and following lung injury induced by saline lavage. MCh induced marked elevations in R(aw), with no significant change in EELV or H at any PEEP. After lavage, the severity of hypoxia was reflected systematically in significant decreases in EELV at all PEEP levels (-42+/-13%, -26+/-4%, and -18+/-5% at 1, 3 and 7 cm H(2)O, respectively), whereas compromised gas exchange was not associated with consistent changes in the mechanical parameters at a PEEP of 7 cm H(2)O (20+/-9% and 14+/-9% in R(aw) and H, respectively; p=0.2). We conclude that R(aw) is the only sensitive indicator for the detection of a compromised lung function during MCh infusions, whereas the estimation of EELV is necessary to follow the progression of a lung injury when a high PEEP level is applied.