Unique intramolecular rearrangement product ions have been observed in the product ion spectra of a number of peptides. Multiple stages of mass analysis (MSn), molecular modeling, and chemical modifications of peptides have been used to provide insight into the mechanism of this rearrangement reaction. The rearrangement process begins with a four-residue immonium ion that transfers a proton from the immonium nitrogen to the primary amine on the N-terminus. The proton transfer leads to the rearrangement of the peptide, exposing an internal amino acid on the terminus of the new ion. The internal amino acid that becomes the terminus of the new ion is then readily lost. The reaction seems to benefit from an extended experimental time frame available for reaction. The reaction is most prominent in quadrupole ion trap and Fourier-transform ion cyclotron resonance experiments,is observed under some conditions in a triple quadrupole, but is not seen in a sector instrument. Without previous knowledge of this process, the peptide sequence as determined by MS/MS could be misidentified.