Inhibitors of Cl⁻ and secretion reduce acetylcholine-induced liquid, but not mucin, secretion by bronchial submucosal glands [S. K. Inglis, M. R. Corboz, A. E. Taylor, and S. T. Ballard. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L372–L377, 1997]. The present study quantified contributions of Cl⁻ and transport to volume and composition of acetylcholine-induced liquid secretion by airway epithelium. When distal bronchi were excised from 33 pigs and treated with 10 μM acetylcholine, the airways secreted 13.4 ± 0.7 μl ⋅ cm⁻² ⋅ h⁻¹. Bumetanide (10 μM) pretreatment reduced acetylcholine-induced liquid and Cl⁻ secretion rates by ∼70%, but secretion fell by only 40%. Dimethylamiloride (DMA; 100 μM) pretreatment reduced Cl⁻ secretion rates by ∼15%, but secretion fell 47%. DMA alone had little effect on liquid secretion. When airways were pretreated with both bumetanide and DMA, acetylcholine-induced liquid secretion was nearly abolished. We conclude that about three-fourths of acetylcholine-induced liquid secretion in distal bronchi is dependent on Cl⁻ secretion. Most of the remaining response is driven by secretion. We speculate that the principal source of this liquid is submucosal glands. Crossover inhibition of bumetanide on secretion and DMA on Cl⁻secretion implies modulation of anion secretion secondary to changes in cell electrolyte composition.