Background: Activation of local and systemic coagulation is a common finding in patients with pneumonia. There is evidence that glucocorticoids have procoagulant activity in the circulation, particularly in the context of inflammation. The effects of glucocorticoids on local pulmonary coagulation have not yet been investigated. Objective: To use a human model of lung inflammation based on the local instillation of endotoxin in order to investigate whether glucocorticoids alter pulmonary coagulation. Methods: Twenty-four healthy volunteers were randomized to receive either dexamethasone or placebo in a double-blind trial. Endotoxin was instilled via bronchoscope into right or left lung segments, followed by saline into the contralateral site. Six hours later, a bilateral bronchoalveolar lavage (BAL) was performed and coagulation parameters were measured. Results: Endotoxin induced activation of coagulation in the bronchoalveolar compartment: the level of prothrombin fragment 1 + 2 (F1 + 2) was increased three-fold (248 pmol L-1, 95% confidence interval [CI] 43-454 versus 743 pmol L-1, 95% CI 437-1050) and the level of thrombin-antithrombin complex (TATc) was increased by similar to 50% (31 mu g L-1 , 95% CI 18-45 versus 49 mu g L-1, 95% CI 36-61) as compared with saline-challenged segments. Dexamethasone reduced F1 + 2 (284 pmol L-1, 95% CI 34-534) and TATc (9 mu g L-1, 95% CI 0.7-17) levels almost to those measured in BAL fluid from the saline-instilled segments in the placebo group. Dexamethasone even profoundly reduced F1 + 2 levels (80%) in saline-instilled lung segments (50 pmol L-1, 95% CI 12-87). In contrast, dexamethasone had no effect on systemic F1 + 2 levels. Conclusions: Dexamethasone inhibits endotoxin-induced coagulopathy in lungs. This trial is the first to provide insights into the effects of glucocorticoids on pulmonary coagulation in response to endotoxin.