Isolated guinea-pig tracheae exposed to conditioned air mucosally and to circulating saline solutions serosally have been subjected to an osmotic gradient between saline and airway surface and to a range of drugs. Experiments were conducted to examine the mechanisms that regulate airway surface liquid during condensation and evaporation. Measurements were made of the depth of airway surface liquid, its sodium activity, the transepithelial potential difference, and of net water and sodium transport across the airway. Results suggest that osmotic gradients have profound effects on airway surface liquid but drugs that influence secretory activity (methacholine, substance P) or ion transport activity (amiloride, bumetanide, oubain) do not.