It is thought that there is little or no change in globular protein conformation upon removal of solvent water. This idea is supported by a number of studies on lysozyme which are consistent with a constant conformation as the protein is taken from aqueous solution to complete dryness. We now report a difference hydrogen- exchange study in which lyophilized lysozyme samples, either completely dry or hydrated at a high relative humidity, were compared with lysozyme in solution. The results provide strong, though indirect, evidence that lysozyme in lyophilized samples cannot have the same conformation as it does in aqueous solution.