A novel strategy for affinity-based surface modification of the conducting polymer, polypyrrole, (PPy), has been developed. A 12-amino acid peptide (THRTSTLDYFVI, hereafter denoted T59) was previously identified via the phage display technique. This peptide noncovalently binds to the chlorine-doped conducting polymer polypyrrole (PPyCl). Studies have previously shown that conductive polymers have promising application in neural electrodes, sensors, and for improving regeneration and healing of peripheral nerves and other tissues. Thus, the strong and specific attachment of bioactive molecules to the surface of PPy using the T59 affinity peptide is an exciting new approach to enhance the bioactivity of electrically active materials for various biomedical applications. We demonstrate this by using T59 as a tether to modify PPyCl with the laminin fragment IKVAV to enhance cell interactions, as well as with the so-called stealth molecule poly(ethylene glycol; PEG) to decrease cell interactions. Using these two modification strategies, we were able to control cell attachment and neurite extension on the PPy surface, which is critical for different applications (i.e., the goal for tissue regeneration is to enhance cell interactions, whereas the goal for electrode and sensor applications is to reduce glial cell interactions and thus decrease scarring). Significantly, the conductivity of the PPyCl surface was unaffected by this surface modification technique, which is not the case with other methods that have been explored to surface modify conducting polymers. Finally, using subcutaneous implants, we confirmed that the PPyCl treated with the T59 peptide did not react in vivo differently than untreated PPyCl. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.