The non-covalent complexes between some DNA-binding drugs and duplex oligodeoxynucleotides were studied by ionspray mass spectrometry, with the aim of evaluating the suitability of this technique to screen rapidly a series of drugs exerting their activity through non-covalent binding to speciΓc base sequences of DNA. Two classes of drugs were considered, distamycins (which show affinity for the minor groove of DNA) and anthracyclines (which interact through intercalation between bases). For the former, was chosen as the model oligo-d(CGCGAATTCGCG) 2 deoxynucleotide. Following optimization of sample preparation and instrumental conditions, the complexes of di β erent distamycins were observed ; depending on the ligand considered, 1 :1 or 2 :1 complexes were formed preferentially. A semi-quantitative evaluation of the relative affinities was made by measuring the ratio of the complexes signals to those of the duplex, and also by competitive binding with equimolar amounts of distamycin. For anthracyclines, the complex was chosen as the model for a preliminary mass spectrometric daunorubicin-d(CGATCG) 2 study ; however, the signals of the duplex and the complex were very low compared with the monomer signal. Since the complex was known to be stable in solution, this was ascribed to gas-phase instability, probably caused by electrostatic repulsion between negatively charged phosphate groups. 1997