We report on a novel method for detecting DNA hybridization, based on the precipitation of silver on gold nanoparticle tags and a subsequent electrochemical stripping detection of the dissolved silver. Such coupling of a nanoparticle-promoted silver precipitation with the remarkable sensitivity of stripping metal analysis offers a dramatic enhancement of the hybridization response. An efficient magnetic isolation of the duplex is used for discriminating against nonhybridized DNA, including an excess of mismatched oligonucleotides. The new silver-enhanced colloidal gold stripping detection strategy holds great promise for the detection of DNA hybridization and represents an attractive alternative to indirect optical affinity assays of nucleic acids and other biomolecules.