The pathology of non-immuno logical airway contraction is not well understood. To define the activation of different phenotypes of mast cells, a rat non-immunological asthmatic model was prepared. Air-way contraction in rats was measured by an unrestrained whole-body plethysmographic system following a 10-min inhalation challenge with a 5% solution of compound 48/80. Histamine, leukotrein C-4 (LTC4) and tumor necrosis factor (TNF)-alpha levels in bronchoalveolar lavage fluid, as well as tissue histamine content were quantified. Mast cells and eosinophils were detected by histology. Both the early and late phase of airway responses were induced by inhalation of compound 48/80. Histamine and TNF-alpha levels increased significantly 30 min after challenge, but no increases were detected at either 8 or 24 h after challenge. A high LTC4 level was detected in 30 min and 8 h after challenge. Tissue histamine content decreased at 30 min after challenge and returned to the unstimulated level by 8 h. Connective tissue mast cells in rat trachea showed a degranulation response. Along with the increase in numbers of mucosal mast cells, rat mast cell protease 11 at both mRNA and protein levels in the trachea epithelial layer was also increased significantly at 30 min after challenge. We conclude that compound 48/80 inhalation causes both the early and late phase of airway contraction in rats. Mast cell degranulation is responsible for the early phase of airway response, which subsequently triggers the late phase of airway response. (c) 2005 Elsevier B.V. All rights reserved.