Surface enhanced resonance Raman scattering (SERRS) is shown to be a satisfying method to study the interaction between DNA and ruthenium complexes [Ru(bpy)2(Hcmbpy)][PF6]2, where Hcmbpy = 4-carboxy-4′-methyl-2,2′-bipyridine. Such metallic complexes are known for their fluorescence properties. To validate this spectroscopic approach we have checked that i) at a given λex, silver colloidal SERRS spectra of Ru complexes closely resemble resonance Raman spectra in aqueous solutions, intensity excepted, and ii) the DNA fragments are not altered when they are adsorbed on the Ag nanoparticles surface. This investigation shows that the intensity of the Ru complexes SERRS spectra is reduced in the presence of DNA, in particular for the specific bands assigned to the Hcmbpy ligand. This collapse demonstrates that the Ru complexes bind DNA through the Hcmbpy moiety, and intercalation is suggested as the binding mode. The DNA binding by the enantiopure Ru complexes (Δ or Λ) is more efficient than by the racemic complexes. © 2006 Wiley Periodicals, Inc. Biopolymers 82:399–404, 2006