Ion and water balance by the in vivo airway epithelium was investigated utilizing dynamic computer modeling. Parameters of the osmotically significant transport processes were varied to assess the sensitivity of water transport and fluid composition to transport perturbations. Establishment and regulation of water secretion represent a coordinated function of at least seven different ion transport processes: basolateral passive potassium transport, basolateral active sodium-potassium transport, basolateral sodium-potassium-chloride cotransport, apical passive sodium and chloride transport, and diffusion of sodium and chloride across the paracellular path. We found that apical chloride permeability at a level reported for cystic fibrosis is sufficient to cause the airway dehydration characteristic of cystic fibrosis. Given the reduction in apical chloride permeability in cystic fibrosis, a reduction in apical sodium permeability can potentially compensate completely for the airway dehydration associated with the cystic fibrosis genetic defect. Other simulations presented here address the importance of various membrane transport processes in airway epithelium water balance and the sensitivity of epithelium water balance to ion transport perturbations.