Solvation of α-chymotrypsinogen A (α-ctg A) in aqueous urea, methylurea, N,N′-dimethylurea and ethylurea was studied by density measurements. From the densities at constant molality and at constant chemical potential the preferential solvation parameters were determined. In urea and methylurea preferential solvation was observed, whereas in N,N′-dimethylurea and ethylurea at higher concentration water is preferentially bound. From preferential solvation data Gibbs free energy of transfer of α-ctg A from water to urea and alkylurea solutions were calculated. Since the enthalpies of transfer were determined previously, the entropies of transfer could also be obtained so that a complete thermodynamic description is available. An attempt is made to interpret the values of the thermodynamic quantities in terms of various interactions involved in solvation as well as to calculate the exchange constant by using the model of weak interactions. In solvation of alkylureas the hydrophobic nature of the alkyl groups is clearly reflected.