The optimal timing of exogenous surfactant application to reduce pulmonary injury and dysfunction was investigated in a rat lung ischaemia and reperfusion injury model. Lungs were subjected to flush perfusion, surfactant instillation, cold ischaemia (4 degrees C, 4 h) and reperfusion (60 min). Animals received surfactant before (group 1) or at the end (2) of ischaemia, or during reperfusion (3) or not at all (4). Control groups included "worst case" without Perfadex and surfactant (5), "no injury" without (6) or with surfactant (7), and ischaemia with pre-ischaemic surfactant (8). Intra-alveolar oedema and blood-air barrier injury were estimated by light and electron microscopic stereology. Perfusate oxygenation and pulmonary arterial pressure (P(pa)) were determined during reperfusion in groups 1 to 4. Intra-alveolar oedema was almost absent in groups 1, 6, 7 and 8, pronounced in 2, 3 and 4, and severe in 5. Blood-air barrier injury was moderate in groups 1 and 8, slightly pronounced in 2, 3 and 4, extensive in 5 and almost absent in 6 and 7. Perfusate oxygenation was significantly higher in group 1 compared with groups 2 to 4. P(pa) did not differ between the groups. In conclusion, exogenous surfactant attenuates intra-alveolar oedema formation and blood-air barrier damage and improves perfusate oxygenation in the rat lung, especially when applied before ischaemic storage.