Water O-17, H-2, and H-1 nuclear magnetic relaxation dispersion (NMRD) data are presented for the Y35G mutant of bovine pancreatic trypsin inhibitor (BPTI) in aqueous solution. The NMRD data show that the three buried water molecules in this protein exchange with bulk water on the time scale of 15 ns to 1 mu s and undergo librational motion of considerable amplitude in the protein cavities. By analysis of the three independent order parameters provided by the NMRD data in terms of an anisotropic harmonic libration model, the amplitude and anisotropy of water rotation in protein cavities is quantitatively assessed. All seven distinct buried water molecules in wild-type BPTI and in the G36S and Y35G mutants are examined in this way. The harmonic libration model also allows the rotational entropy of buried water molecules to be deduced from the experimental order parameters. Although each of the investigated buried water molecules is engaged in three or four hydrogen bonds, their entropies span the full range from ice to bulk water, suggesting that the hydration of protein cavities with weaker hydrogen-bonding capacity may be entropically driven. This might be true also for weakly hydrogen-bonded water molecules in surface clefts, thus reversing the conventional view that ligand binding to proteins is entropically favored by release of ordered water.