A study of acid- and base-catalyzed hydrogen isotope exchange of bicyclo[2.2.1]heptan-2-one (1a) and its 3-deuteriated analogs has been carried out. We find that the kexo/kendo ratio (658 ± 66) for deuteroxide-catalyzed H → D exchange of 1a at C-3 is 7.2 ± 1.5 times greater than the kexo/kendo ratio (91 ± 9) for hydroxide-catalyzed D → H exchange of 1b. For acid-catalyzed exchange in CH3COOD(H)–D(H)Cl the rate ratios are 156 ± 20 and 29 ± 2 for H → D and D → H exchange, respectively. Equations which relate the observed selectivity kexo/kendo (kfast/kslow) to the intrinsic selectivity and the primary, secondary, and solvent KIEs are developed. The differences between the rate ratios for H → D and D → H exchange are interpreted on the basis of a significant contribution of an inversion pathway to exchange of the slow proton (deuteron). The significance of our study – it relates to the mechanism of hydrogen isotope exchange of diastereotopic protons (deuterons, tritons) of any carbon acid – is discussed.