The α and β subunits of the amiloride-sensitive rat epithelial sodium channel (αβENaC) were expressed in the yeast Saccharomyces cerevisiae. We used a combination of yeast strains, including a mutant in the secretory pathway (sec6), and Western blotting techniques, to show that αβENaC was synthesized and targeted through the secretory system to the plasma membrane. Yeasts expressing αβENaC were more sensitive to salt than the parent strain. In addition, amiloride, a specific blocker of ENaC, was found to suppress salt sensitivity in the yeast strain expressing αβENaC.