Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), the most common autosomal recessive disorder in Caucasians. The ion transport by airway epithelia from CF patients is abnormal and characterized by a reduced Cl- secretion and an accelerated Na+ absorption by the human amiloride-sensitive epithelial sodium channel (hENaC). The molecular mechanisms leading to the functional Na+ hyperabsorption are only partly understood. This prompted us to investigate whether defects on the molecular level could be due to the Na+ transport abnormality in CF. Therefore, we cloned and sequenced all three ENaC subunits (a, b, [gamma]) from CF and non-CF nasal tissue. We found no striking sequence- related differences but identified some polymorphisms. Furthermore, we measured the expression of all three human nasal ENaC (hnENaC) subunits in CF and non-CF tissue. We showed via real-time PCR that the mRNA amount of the hnENaC subunits in CF tissue is increased. Similarly, we investigated with Western blot analyses the presence of hnENaC in both groups. The protein abundance of the a- and b-hnENaC seems to be increased in contrast to a decreased [gamma]-hnENaC in CF epithelia. From these data we assume that the Na+ hyperabsorption could be due to an increased hnENaC expression in CF patients causing severe lung symptoms.