Preformed and newly generated mediators released from airway mast cells may play a role in adenosine-induced bronchoconstriction. To investigate the possible role of mast-cell-derived mediator release in mediating bronchoconstriction induced by adenosine 5'-monophosphate (AMP), we have examined the fluid obtained by bronchoalveolar lavage for inflammatory mediators and markers of airway permeability immediately after instillation of AMP directly into an airway segment of 10 asthmatic subjects. Eight subjects completed the protocol. When compared with the saline-challenged segment, the response to endobronchial stimulation with AMP was characterized by a prompt reduction in airway caliber paralleled by a significant rise in PGD2, histamine, and tryptase levels in the lavage fluid. After AMP challenge, the median (range) concentration for PGD2 increased from 36 to 205 pg/ml (p = 0.006), for histamine from 184 to 433 pg/ml (p = 0.018), and for tryptase from 0.30 to 0.54 ng/ml (p = 0.013). In addition, a small but significant rise in albumin levels (from 27.8 to 36.1 micrograms/ml; p = 0.031) was detected after endobronchial challenge with AMP. These findings indicate that adenosine-induced responses may be initiated by the acute release of mast-cell-derived mediators, including PGD2, histamine, and tryptase.