cAMP-elevating agents such as forskolin and vasoactive intestinal peptide induce liquid secretion by tracheobronchial submucosal glands. This pathway is thought to be CFTR dependent and thus defective in cystic fibrosis; however, the ionic mechanism that drives this secretion process is incompletely understood. To better define this mechanism, we studied the effects of ion transport inhibitors on the forskolin-induced liquid secretion response (J_v) of porcine distal bronchi. The forskolin-induced J_v was driven by a combination of bumetanide-sensitive Cl⁻ secretion and DIDS-sensitive HCO₃⁻ secretion. When Cl⁻ secretion was inhibited with bumetanide, Na⁺/H⁺ exchange-dependent HCO₃⁻ secretion was apparently induced to compensate for the loss of Cl⁻ secretion. The forskolin-induced J_v was significantly inhibited by the anion channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, and glibenclamide. We conclude that the forskolin-induced J_v shares many characteristics of cholinergically induced secretion except for the presence of a DIDS-sensitive component. Although the identity of the DIDS-sensitive component is unclear, we speculate that it represents a basolateral membrane Na⁺-HCO₃⁻ cotransporter or an Na⁺-dependent anion exchanger, which could account for transepithelial HCO₃⁻ secretion.