The effect of temperature and pH on thermoinactivation kinetics of glucose dehydrogenase from Haloferax mediterranei has been studied in the presence of different monovalent sails (LiCl, LiBr, NaCl, NaBr, KCl, KBr, NH4Cl, and NH4Br) and polyols (glycerol, erythrytol, xylitol, and sorbitol) concentrations. The stabilization degree of salts followed the rank of the Hofmeister series, and the product of the Setchenov constant (K-s) times the concentration of solute (C-s) was useful to predict the enzyme stability in the presence of salt solutions. Polyols stabilized the halophilic enzyme as much as salts. For an equal polyol concentration, the thermostability increased in the range glycerol < erythritol < xylitol < sorbitol. The overall hydroxyl group concentration proved to be a good parameter for correlating the protective effect of polyols with the polyol nature. Thermoinactivation of the halophilic glucose dehydrogenase in the presence of NaCl and sorbitol was compared with that of a nonhalophilic glucose dehydrogenase in terms of the transition state theory . The free activation energy was, in all cases, enthalpy driven, and hydrogen-bond and/or ionic-binding interactions are the main forces involved in protein stabilization. The halophilic enzyme showed, in general, lower free activation energies for the deactivation process. The adaptation of the enzyme to a halophilic environment led to an enzyme with higher activity at high salt concentrations, but such an increase in enzyme activity was not related to an enhancement in enzyme thermostability.