The effects of partial replacement of bathing solution sodium by potassium on potential difference, conductance and ion transport of canine tracheal epithelium were studied in Ussing chambers. Whereas up to 100 mmol/l mucosal K+ had no effect, raised serosal [K+] induced a concentration dependent decrease in transepithelial potential difference and increase in conductance. When serosal K+ was 100 mmol/l, the potential difference fell 30 mV to 1.1 +/- 1.0 mV and conductance rose 4.5 mS/cm2 to 6.6 +/- 0.9 mS/cm2. Seventy-five percent of the K+ induced conductance required Cl- (120 mmol/l) in the luminal bathing solution. Unidirectional Cl- fluxes were increased by raised serosal K+ but 14C-mannitol permeability was unchanged. The increased unidirectional Cl- flux induced by high K+ exposure was inhibited by luminal exposure to diphenylamine-2-carboxylic acid (DPC) or other chloride channel blockers, but was not inhibited by loop diuretics. These results suggest that in the presence of 100 mmol/l serosal K+ the transcellular chloride conductance of tracheal epithelium was increased. Increased chloride conductance of the apical cell membrane contributed to the raised transcellular permeability, but the route across the basolateral cell membrane was not identified.