The gas-phase reactions between urea and Ca2+ have been investigated by means of electrospray mass spectrometry techniques. The MS/MS spectra of [Ca(urea)](2+) and [Ca(urea-H)](+) complexes show that both ions decompose by losing NH3 and HNCO. However, for the [Ca(urea)](2+) system, additional intense peaks are observed at m/z 44, 56, and 82. Density functional theory calculations at the B3-LYP/cc-pWCVTZ level have been used to help rationalize these observations through an examination of the structures and bonding characteristics of the various stationary points on the [Ca(urea)](2+) and [Ca(urea-H)](+) potential energy surfaces (PESs). Analysis of the topology of these PESs allows mechanisms to be proposed for the loss of NH3 and HNCO. In addition, for [Ca(urea)](2+), the calculations suggest that the m/z 44, 56, and 82 peaks correspond to H2NCO+, CaNH2+, and [Ca, N, C, O](+), respectively, which are produced in Coulomb explosion processes. The unimolecular reactivity of [Ca(urea-H)](+) differs from that of [Ca(urea)](2+) largely through the absence of the Coulomb explosion fragmentations. Urea behaves as an oxygen base with respect to Ca2+, the calculated binding energy being 453 kJ mol(-1).