The purpose of this study was to test whether cough response to inhaled ultrasonically nebulized fluid is dependent on the ionic content of the fluid. Coughing was recorded in human volunteers during inhalation of aqueous solutions in a series of double blind randomized experiments. The occurrence of cough was found to be dependent on the concentration of chloride ions in the inhaled fluid, cough frequency progressively increasing as chloride ion concentration was reduced. It is proposed that the ion composition of the surface lining fluid of the airway may moderate the cough response by means of a chemo-receptor, although tonicity may also be important.