Electrospray ionization with in-source collisionally induced dissociation has been used to probe the gas phase stability of an oligonucleotide duplex and its complexes with some minor groove binding drugs. On the basis of the arguments developed in detail by Drahos et al. (J. Mass Spectrom. 1999; 34:1373), this type of experiment can also be described as ‘thermal denaturation in the gas phase’. We found that the gas phase denaturation curves were very similar to the solution phase denaturation curves determined by the traditional UV spectrophotometric method and, by analogy with the melting temperature Tm which characterizes the stability in solution, we define a melting voltage Vm to characterize the stability in the gas phase. A comparison of the Tm and Vm relative values suggests that the structure of the complexes is conserved during the electrospray process which transfers the ions from the solution to the gas phase. Copyright © 2000 John Wiley & Sons, Ltd.