Processes such as conformational phase transitions, ligand binding events, and enzymatic catalysis alter the structure of proteins as well as the nature of their solvent accessible surface. Consequently, these processes result in corresponding changes in the sound velocity of the protein solution. As is shown by the example of two typical globular proteins, cytochrome c and α-chymotrypsinogen A, the transition from the native state to the molten globule state is accompanied by an increase in sound velocity, while the native state–unfolded state transition is accompanied by a decrease in sound velocity. The interpretation of the macroscopic sound velocity data for the different phase states of proteins in terms of microscopic structural and hydrational differences is a very sophisticated problem. One of the ways of attempting to solve the problem of distinguishing between the contributions of protein structure and hydration to the sound velocity is to search for correlations between the structural crystallographic data of a large number of globular proteins and their ultrasonic velocimetric characteristics.