Abstract The hydrogen/deuterium (H/D) exchange of gas‐phase ions of holo‐ and apo‐myoglobin has been studied by confining the ions in a linear quadrupole ion trap with D 2 O or CD 3 OD at a pressure of several mTorr. Apo‐myoglobin ions were formed by collision‐induced dissociation of holo‐myoglobin ions between the orifice and skimmer of the ion sampling system. The exchange takes place on a time scale of seconds. Earlier cross section measurements have shown that holo‐myoglobin ions can have more compact structures than apo‐myoglobin. Despite this, both holo‐myoglobin and apo‐myoglobin in charge states +8 to +14 are found to exchange nearly the same number of hydrogens ( ca . 103) in 4 s. It is possible the ions fold or unfold to new conformations on the much longer time scale of the exchange experiment compared with the cross section measurements. Copyright © 2002 John Wiley & Sons, Ltd.