Our statistical-mechanical formulation for calculating heat-capacity and enthalpy functions in conformational changes of biomolecules is extended to include free-energy and entropy functions and generalized to treat multidomain systems. Each conformant may consist of one or several independent sections or domains. The treatment is based on a two-state model in which all residues within a domain are fully cooperative. The thermodynamic functions can be evaluated from the ratio of the effective partition functions of the residues in the different conformants, the difference in their zeros of energy, and the temperature derivatives of these partition functions. The former two parameters were evaluated from published optical density data of the conformants within the transition region; the last item was obtained from published heat-capacity data of the pure conformants outside the transition region. Three types of thermodynamic functions were considered: (I) total functions, which include contributions from both folded (conformant A) and unfolded (conformant B) states: (2) excess functions, which are the functions in excess of pure A; (3) conformational functions, which do not include contributions from either pure A or pure B. The theory was applied to solutions of ribonuclease, exemplifying single-domain systems, and to solutions of poly-gamma -benzyl-L-glutamate, exemplifying multidomain systems. All thermodynamic functions, including the heat capacities, in the transition region were calculated. The results are compared with published experimental values and are in reasonably good agreement with the measured results. The excess and conformational thermodynamic functions are compared and discussed.