The potential energy hypersurface of protonated formamide has been investigated. Using a dual-cell Fourier transform mass spectrometer, proton-transfer experiments with formamide were performed. From these experiments the activation energies for the three unimolecular reactions observed, (i) loss of water, (ii) loss of ammonia, and (iii) loss of carbon monoxide, were determined. Using a four-sector mass spectrometer, the fragmentations of metastable protonated formamide ions were observed. The results of all experiments, supported by high-level ah initio quantum chemical calculations and RRKM calculations, provide a consistent reaction model. The reaction paths for loss of water and loss of ammonia depart from the most stable O-protonated isomer, while the somewhat less stable N-protonated isomer is the precursor for CO loss. The significance of the gas-phase chemistry of protonated formamide to the solution phase is discussed.