Charge detection mass spectrometry in combination with a linear electrostatic ion trap coupled to a continuous wavelength infrared CO2 laser has been used to study the multiphoton dissociation of DNA macromolecular ions. Samples, with masses ranging from 2.23 to 31.5 MDa, include single strand circular M13mp18, double strand circular M13mp18, and double strand linear LambdaPhage DNA fragments. Their activation energies for unimolecular dissociation were determined. Activation energy values slightly increase as a function of the molecular weight. The most important result is the difference between the fragmentations observed for hybridized double-strands and dimers of single strands.