Acute lung injury (ALI) and ARDS are difficult to manage and associated with substantial mortality. Suitable models are required in early clinical drug development to bridge the gap between preclinical experiments and clinical trials in severely ill patients. The aim of this trial was to validate bronchial endotoxin instillation as a model of early onset ALI by studying the anti-inflammatory and anti-edema effects of dexamethasone. We hypothesized that dexamethasone would decrease lung inflammation and ensuing vascular leakage. Twenty-four healthy young volunteers received dexamethasone twice (20mg iv. at -13h and -1h) in a randomized, double-blind, placebo controlled trial and volunteers had endotoxin (4 ng/kg) instilled into a lung segment and saline instilled into a contralateral segment at 0h, followed by bronchoalveolar lavage (BAL) at 6 h. Non-parametric statistical tests were applied. Endotoxin increased tumor necrosis factor levels from a median of 0.5 pg/mL 200-fold to 100 pg/mL in BAL samples (pConclusions: Dexamethasone effectively prevented LPS-induced vascular leakage and protein accumulation in the lung. Despite pronounced systemic anti-inflammatory effects, dexamethasone was comparably less effective in preventing IL-6 release from lung into BAL. The model lends itself for proof of concept studies of new drugs which target acute lung inflammation.