SERS spectra of the potent antitumour agent mitoxantrone in aqueous hydrosol and in the hydrosol prepared from deuterium oxide and of its complexes with DNA have been recorded and compared with the corresponding preresonance Raman (pre-RR) and FT-SERS spectra of the same species. SERS and pre-RR spectra obtained at the same excitation wavelength and at concentrations of 5 x 10(-8) and 5 x 10(-5) M, respectively, were found to be nearly identical both in the frequencies and the relative intensities of the bands. Moreover, interactions between the drug and calf thymus DNA induced identical effects in the pre-resonance Raman, surface-enhanced Raman scattering (SERS), and Fourier transform SERS spectra of the drugs. An analysis of these spectral changes showed that an interaction involves preferential intercalation of the ring A and, in part, ring B of the chromophore inside the DNA double-stranded helix. The structural specificity of the mitoxantrone intercalation has been studied by SERS analysis of the complexes between the drug and DNA duplexes [d(CpG)(9)](2) and [d(ApT)(9)](2). Mitoxantrone was found to be intercalated preferentially within the CG-rich regions of the double-stranded helix. The data show that the adsorption of the drug/DNA complex on the surface of silver hydrosol does not induce detectable perturbations of the molecular interactions within the complex and thus demonstrate the applicability of SERS for the analysis of drug/DNA interactions under conditions preserving the structure of the complexes and at extremely low concentrations.