A new and simple electrochemical method capable to detect single-base mutations in DNA has been developed. It relies on the electrocatalytic oxidation of NADH by the intercalator Brilliant Cresyl Blue (BCB). Whereas negligible catalytic responses were obtained with graphite electrodes modified by BCB-single-stranded DNA, high catalytic activity is obtained at electrodes modified by the complexes between double-stranded DNA and BCB. The proposed explanation for these results is that charge transport from the intercalated BCB through the DNA base stack is a necessary event for the electrocatalytic activity as disruption by a single-base mismatch leads to a complete suppression of the electrocatalytic voltammetric response. These finds open new possibilities for the detection of DNA hybridization and mutation. (C) 2004 Elsevier Ltd. All rights reserved.