Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which functions as a Cl^-channel. In a small number of patients a mutation can be identified only in one CFTR allele. In these patients other factors, e.g. enhanced activity of the epithelial sodium channel (ENaC), may contribute to the disease. We report about a patient with atypical CF who was found to be heterozygous for the CFTR mutation M952T, heterozygous for the CFTR polymorphism M470V, and heterozygous for a polymorphism (bG589S) in the b-subunit of ENaC. We used the Xenopus laevis oocyte expression system to compare the function of wild-type and mutant/polymorphic channels. The whole cell Cl^-conductance stimulated by IBMX and forskolin was largely reduced in oocytes expressing M470/M952T (9.8±2.1mS) or V470/M952T (7.5±1.6mS) compared to control oocytes expressing M470 (55.2±6.3mS) or V470 (39.7±4.5mS), respectively. The bG589S polymorphism had no significant effect on amiloride-sensitive ENaC currents and therefore is unlikely to contribute to the CF phenotype of the patient. In conclusion we have shown that the M952T mutation largely compromises CFTR chloride channel function.