Microvascular extravasation, lamina propria flooding and luminal entry of plasma are key features of airway inflammation. We have suggested that the extravasated plasma moves across the epithelial lining along hydrostatic pressure gradients. The present study, involving healthy subjects, tests this hypothesis by examining effects of experimentally applied negative and positive luminal pressures on nasal output of plasma at baseline and at histamine-induced plasma exudation. The negative (-10 cmH2O) and positive (10 cmH2O) pressures were applied for 10 min after nasal spray administrations of diluent (saline) and histamine (0.5 mg). The mucosa was then lavaged and the lavage fluid levels of alpha2-macroglobulin were measured as index of plasma exudation. Nasal administrations of diluent and histamine (0.5 mg) were also carried out without any pressure applications. Histamine produced significant mucosal exudation of plasma. The negative luminal pressure augmented this response significantly as well as the baseline appearance of alpha2-macroglobulin in mucosal surface liquids. We conclude that extravasated plasma may be moved across the epithelium by a hydrostatic pressure-operated epithelial mechanism.