A conjugated polymer can be considered as tri-dimensional network of intrinsically conducting macromolecular wires, able to transport signals. When further functionalized with prosthetic groups showing recognition properties, such polymer architecture mimics the nervous system existing in Living beings. With this aim, we have developed a new type of electrochemical sensors, based on electroactive polypyrrole functionalized with oligonucleotide (ODN). At first, we analyzed the experimental conditions for building such modified electrode, showing a high electroactivity in aqueous medium. We developed a new route for the functionalization of polypyrrole, involving a precursor polypyrrole bearing an easy leaving eater group, on which an amino-labelled ODN can be directly substituted. The electrochemical response of this polypyrrole electrode functionalized with an ODN probe has then been analyzed in various aqueous media, containing either complementary or noncomplementary ODN targets. Results show that the cyclic voltammogram of ODN-functionalized polypyrrole is not modified when in presence of a noncomplementary ODN in solution. On the other hand, a significant modification of the voltammogram is observed upon addition of a complementary ODN target, to the electrolytic medium, which indicates that specific hybridization has occurred between the polypyrrole-grafted ODN probe and its complementary ODN target in solution. This biological recognition can be quantitatively determined by an amperometric analysis, and the limit of detection of this electrochemical biosensor is about 10(-11) mel, without any signal processing. These results confirm that functionalized polypyrroles act as macromolecular wires able to transduce biological information into molecular signals. (C) 1999 Published by Elsevier Science S.A. All rights reserved.