To determine the role of neutrophil elastase in allergen-induced airway microvascular leakage, we assessed vascular permeability of guinea pig trachea by measuring the extravasation of Evans blue dye in the circulating blood. Inhalation of ovalbumin (OA) to guinea pigs sensitized with OA caused Evans blue extravasation, indicating an increased microvascular permeability. Pretreatment with ONO-5046 a specific inhibitor of neutrophil elastase, inhibited OA-induced vascular leakage in a dose-dependent manner. Tracheal instillation of human neutrophil elastase likewise increased microvascular permeability, and this effect was almost completely abolished by ONO-5046. Challenge with OA increased the number of neutrophils and neutrophil elastase activity in the bronchoalveolar lavage fluid, and these effects were inhibited by ONO-5046. These results suggest that neutrophil accumulation into the airway and the subsequent release of neutrophil elastase may play a role in the airway microvascular leakage produced by antigen challenge.