The underlying pattern of lung injury in patients with the adult respiratory distress syndrome (ARDS) may be nonuniform. The purpose of this study was to document whether a nonuniform pattern of lung injury influences treatment responses to aerosolized exogenous surfactant. Adult sheep underwent either total lung lavage (Tot Lav) or partial lung lavage (Par Lav) with saline, and they were subsequently mechanically ventilated for 90 min. Previous studies confirmed that this procedure induces acute lung injury. Partial lavage animals had their right upper lobe (RUL) protected from lavage by balloon obstruction of the RUL bronchus, and the occlusion was removed prior to the ventilatory period. Animals in both groups were then treated with either nebulized surfactant (Neb Surf) or nebulized saline (Neb Saline) for a further 180 min. PaO2, PaCO2, and peak inspiratory pressure significantly improved for the Tot Lav-Neb Surf animals compared with pretreatment values (p < 0.01). There were no significant changes for the other three groups (Tot Lav-Neb Saline, Par Lav-Neb Surf, Par Lav-Neb Saline). Lobar distribution of aerosolized [3H]surfactant in lung tissue revealed that Par Lav-Neb Surf animals had approximately 50% of the total surfactant recovered from the RUL compared with approximately 20% recovery from the RUL in the Tot Lav-Neb Surf group. The preferential deposition of exogenous surfactant in the RUL of the Par Lav-Neb Surf group resulted in significantly less surfactant deposited in other injured regions of the lung (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)