Changes in the structural stability of lysozyme, upon adsorption to silica and gallium arsenide (GaAs) surfaces, are studied using a combination of hydrogen/deuterium exchange and matrix-assisted laser desorption/ionization mass spectrometry, This relatively new method offers a tool for directly monitoring the structural stability of adsorbed proteins and generates values for the stabilization energy of proteins and their domains in the adsorbed state, The adsorption and desorption kinetics of lysozyme on silica and GaAs surfaces are monitored with ellipsometry, From the adsorption kinetics it can be inferred that lysozyme adsorbs somewhat faster and in slightly higher amounts onto GaAs than on silica. The average Gibbs free energy required to open the lysozyme structure in solution (5.7 kcal/mol) is only slightly reduced upon adsorption onto silica, resulting in a Gibbs free energy of 5.4 kcal/mol, Adsorption onto GaAs surfaces results in a larger decrease in the stability of lysozyme, Moreover, a distinct difference in the stability within the lysozyme molecule is observed. Whereas one part of lysozyme adsorbed onto GaAs has an average structural stability of -5.5 kcal/mol, an approximately equally large part of the molecule has a stability of -3.7 kcal/mol,