Electrospray ionization mass spectrometry and 1H NMR spectroscopy were used to examine the reactions of cis-[RuCl2(DMSO)4] and trans-[RuCl2(DMSO)4] with deoxynucleosides. Both complexes react with 2′-deoxyguanosine to give identical products, two diastereoisomers containing a single nucleoside coordinated to ruthenium, and a bis adduct containing two coordinated nucleosides. Coordination of the nucleoside to ruthenium is via the N-7 atom in each complex. Trans-[RuCl2(DMSO)4] reacts with 2′-deoxyadenosine to give a pair of diastereoisomers in which the nucleosides are coordinated via their N-1 atoms. Cis-[RuCl2(DMSO)4] reacts less extensively with 2′-deoxyadenosine to give a mixture of products, each of which contains a single 2′-deoxyadenosine ligand coordinated to the metal through the N-1 atom. Trans-[RuCl2(DMSO)4] was found to react only to a small extent with 2′-deoxycytidine under conditions similar to those used for 2′-deoxyguanosine and 2′-deoxyadenosine, and not at all with thymidine, even after prolonged periods. The implications of these results for the mechanisms of antitumour activity of these two complexes are discussed. © 1998 Elsevier Science S.A. All rights reserved.