Background: Application of exogenous surfactant has been proposed to ameliorate lung ischemia-reperfusion injury. Experimentally, donor pretreatment has been favored over posttransplant application. We now report on the first prospective randomized clinical study of donor surfactant instillation in lung transplantation.Methods: Lung donors were randomly assigned to the surfactant (Surf, n=14) or the control group (Co, n=15). Bovine surfactant (100 mg/kg BW) was instilled segmentally via bronchoscopy within 30 min before organ harvest. Diagnostic bronchoalveolar lavage (BAL) was performed before surfactant instillation and 8 h after reperfusion of the graft. Surface-tension lowering properties of surfactant and the ratio of small to large surfactant aggregates (SA/LA) were determined as indicators for preservation of surfactant function from BAL fluid. Clinical outcome of the surfactant group was compared to 187 consecutive cases with otherwise similar treatment.Results: Surface tension of BAL fluid after transplantation was slightly increased in the Surf group but markedly increased in the Co group, indicating loss of surfactant function (9.6±2.1 vs. 17.5±1.9 mN/m; Surf vs. Co, respectively; P<0.05). The SA/LA ratio, as a marker for metabolic conversion of the surfactant material, was high in both groups before explant (0.86±0.4 vs. 0.78±0.31). This ratio was improved after transplant in Surf lungs, but further deteriorated in controls (0.42±0.28 vs. 1.58±0.44). Early clinical outcome showed no death in both groups and was without significant differences between groups due to low sample size, but when compared to our overall recipient population, spirometry in the Surf group revealed higher FEV1 2 weeks after transplant (2.81±0.71 vs. 1.77±0.91; P<0.05).Conclusion: Exogenous surfactant is safe and markedly improves post transplant surfactant function. Its application before organ harvest is therefore encouraged, especially in borderline donors.