Introduction: The overload-hypertrophy of the heart is associated with many changes of the cellular phenotype, which result in an enhanced risk for fatal arrhythmias. Experiments on rats with cardiac overload-hypertrophy proposes an induction of the "transient outward current", which is coded beside others by the Kv1.4-potassium channel, an important determinant of the repolarisation phasis 1 of the action potential. The "cystic fibrosis transmembrane conductance regulator" (CFTR) conducts the repolarising, PKA activated, outward rectifying chloride current. Both channels can affect the action potential duration. Methods: The mRNA-expression was quantified by standard calibrated competitive reverse transcription polymerase chain reaction. We investigated right atrial myocardium, obtained during connecting the heart-lung-machine in elective cardiac surgery and left ventricular myocardium from explanted hearts and not-implantable donor-hearts. Results: The left ventricular CFTR-mRNA expression in non-failing donor hearts was 52 ±10 amol/mg RNA (n=7). Terminal failing ventricles without ACE-inhibitor therapy had a significantly reduced mRNA-expression of 24 ±9 amol/mg RNA (n=5). In contrast, the mRNA of failing ventricles with ACE-inhibitors was with 56 ±8 amol/mg RNA (n=9) in the range of donor hearts. The right atrial CFTR-mRNA expression in heart failure under therapy with Ca2+-antagonists was 33 ±14 amol/mg RNA (n=8). Without dilatator therapy the expression was 38 ±5 amol/mg RNA (n=27). Under therapy with ACE-inhibitors the CFTR-expression was enhanced to 59 ±9 amol/mg RNA (n=16). The left ventricular Kv1.4-mRNA in nonfailing donor hearts was 22 ±4 amol/µg RNA (n=6). In failing ventricles without ACE-inhibitor therapy the expression was enhanced to 51 ±9 amol/µg RNA (n=5). In contrast, failing ventricles with ACE-inhibitor therapy had a reduced expression (30 ±6 amol/µg RNA (n=7)), which was nearly in the range of the donors. Conclusion: In heart failure the left ventricular mRNA-expression of the CFTR is reduced and the mRNA of the Kv1.4 is enhanced. The therapy with ACE-inhibitors can normalise the mRNA expression of both channels. These results implicate an involvement of the regulation of both channels in the enhanced risk for arrhythmias and in the preventive potential of the ACE-inhibitor therapy in heart failure. In the human heart the exon 5-positive CFTR-mRNA is dominating.