The label-free detection of oligonucleotides of 12-14 bases at a concentration of 10 −7 M (double helix) was achieved by using surface enhanced Raman scattering (SERS) and spermine as the aggregant of Ag sol. The wavenumbers of the produced SERS spectra of DNA are similar to those in the corresponding normal Raman spectra of free DNA, allowing the detailed assignment of the vibrational modes. The conformation of the adsorbed DNA, the adsorption geometry, and a molecular model of the interactions among DNA, spermine, and Ag nanoparticle are derived from the SERS spectra. The results show that the protonated amine groups of spermine interact with phosphodioxygens of DNA and N7s of dA and dG from the major groove. The protonated amines are also attracted to the negatively charged Ag surface and thus induce the adsorption of DNA on the metal surface. The DNA remains mostly in the B-conformation with a variation in the C5 -O dihedral angle. DNA lies flat with the bases perpendicular to the metal surface.