Eosinophil major basic protein (MBP) is a granule-associated cytotoxic protein found in sputum and deposited on airway tissues of patients with acute asthma. We therefore studied the effect of human MBP on ion transport in dog tracheal epithelium. We mounted the posterior tracheal membranes of mongrel dogs in Ussing chambers and measured potential differences across the membranes and short-circuit current. Using 22Na+ and 36Cl- as tracers, we determined net ion movements. The addition of MBP (5 X 10(-6) M) to the mucosal, but not to the serosal, side of the membranes produced an increase in short-circuit current from 2.25 +/- 0.19 (mean +/- SE) to 2.78 +/- 0.23 muEq.cm-2h-1 (p less than 0.0001) and in net chloride secretion from 1.57 +/- 0.22 to 2.31 +/- 0.24 muEq.cm-2h-1 (p less than 0.01). There was no change in net sodium movement. Pretreatment with indomethacin (10(-5) M) attenuated, but did not abolish, the increase in short-circuit current. After exposure to MBP, prostaglandin E2 release into the serosal bathing solution increased from 10.0 +/- 4.2 to 17.0 +/- 6.9 ng.cm-2h-1 (p less than 0.05). The results of this study indicate that MBP simulates prostaglandin E2 production and chloride secretion by dog tracheal epithelium. Thus, eosinophils in the airways, through release of MBP, may affect mucociliary clearance by changing the volume and composition of respiratory tract fluid.