Desorption electrospray ionization (DESI) is implemented on an Orbitrap mass spectrometer. The ion source is described and applications which utilize the high-resolution capabilities of the Orbitrap are emphasized, including the characterization of peptides and active ingredients in pharmaceutical tablets. Measurements are made in less than 1 s at a resolution of 60 000. The implications of the data for the mechanisms of DESI are discussed. Copyright © 2006 John Wiley & Sons, Ltd.