A fluorogenic, nucleic acid directed, Cu+-catalyzed chemical reaction was developed that allows sequence-specific detection of nucleic acids at concentrations as low as 20 nM through monitoring of the increase of the fluorescence intensity. A single nucleotide mismatch in the template strand leads to the complete inhibition of this reaction. We observed that a Cu+ ion stabilized with a water-soluble ligand is a significantly more efficient catalyst than free Cu+.