Mass spectrometry (MS) methods involving gas-phase fragmentation hold considerable promise for analyzing regioselective deuteration patterns of proteins following solution-phase amide hydrogen exchange (HX). However, the general viability of such an approach is questionable due to the possible occurrence of intramolecular hydrogen migration ("scrambling"), which tends to randomize or distort the spatial isotope distribution. Rand et al. (J. Am. Chem. Soc. 2008, 130, 1341-1349) have recently reported the application of electron capture dissociation (ECD) for measuring deuteration patterns of short peptides with very little scrambling by FT-MS. The current work shows that even much larger systems such as the 76-residue protein ubiquitin can be successfully analyzed by ECD following solution-phase HX. The resulting c and z. ion deuteration levels are in remarkable agreement with previous NMR data, demonstrating that the extent of scrambling and/or other gas-phase artifacts is negligible. These results open the door to future experiments on the folding, structure, and dynamics of proteins by HX/ECD-FT-MS.