Fourier transform infrared spectroscopy was used to study the thermally induced conformational transitions undergone by lysozyme adsorbed to different lipid layers. The role of the electrostatic interaction in protein adsorption and thermal denaturation was investigated by considering the interaction of this protein, which at pH 7.0 carries a positive charge, with anionic, zwitterionic, and cationic lipid layers. There are qualitative and quantitative differences between both the unfolding and the formation of intermolecular beta sheets undergone by lysozyme adsorbed to the different lipid surfaces. Unfolding is a very rapid process at an electrostatically repulsive surface, whereas it is much slower at an electrostatically attractive surface. In all cases, however, lysozyme is destabilized with respect to thermal denaturation as compared to the behavior in bulk solution. The intermolecular beta-sheet formation, which in the bulk has been associated with aggregation and the formation of amyloid fibrils, is also seen to occur at much lower temperatures than is seen for lysozyme in bulk solution. The extent of this surface aggregation was also found to be highly dependent on the surface chemistry. Aggregation at an electrostatically attractive surface goes to an extent similar to that seen for lysozyme in free solution, but it is inhibited at the zwitterionic and cationic surfaces. These results emphasize that the thermal stability and propensity of a protein to misfold can be strongly influenced by the character of the surface with which it interacts.