Transition metal ion-neutral peptide complexes produced by electrospray ionization (ESI) were studied by tandem mass spectrometry with regard to their metal binding structure. Zn2+, Co2+ and Ni2+-histidine containing peptide complexes dissociate at histidine sites upon collisional activation, indicating metal ion binding primarily at the histidine site. The Cu2+-neutral peptide complexes, however, dissociate to product an ion by losing CO2 from the C-terminus, and other product ions by reactions at the C-terminus, suggesting the association of Cu2+ with the peptide C-terminus.