Two methods for gas phase hydrogen/deuterium exchange have been developed for the analysis of small molecules. Hydrogen/deuterium exchange has been implemented by making simple modifications to the plumbing for the nebulizer and curtain gases on a nebulization-assisted electrospray ion source. The nebulizer gas exchange method has demonstrated deuterium exchange levels of 84-97% for a variety of molecules representing a wide range of structural classes containing up to 51 potentially exchangeable hydrogens; this allowed determination of the number of exchangeable hydrogens for all of the molecules studied containing ≤ 25 labile hydrogens (M r ≤ 3000). ND3 gas consumption is minimized in the nebulizer method by toggling the nebulizer from air to ND3 for only a few scans of the total sample elution period. The curtain gas exchange method is more variable, yielding exchange levels of 32-98% for the same set of molecules; this was still sufficient to allow determination of > 70% of the molecules studied containing ≤ 25 labile hydrogens. Gas consumption is minimized in the curtain method by replacing ≤ 10% of the curtain gas flow with ND3. Neither the nebulizer nor curtain exchange method requires the use of deuterated or aprotic solvents at typical 2 μL/min flow rates.