The thermal denaturation of S-protein is investigated at pH 7.0 by means of DSC measurements. The process is reversible and can be assimilated to a two-state transition. The low values of denaturation temperature and enthalpy, between 38.5 and 40.0 °C and 165 and 180 kJ mol-1, respectively, demonstrate that the loss of S-peptide strongly decreases the structural stability. The interaction between S-peptide and S-protein is thermodynamically characterized, at pH 7.0, by studying the thermal stability of S-peptide/ S-protein complexes at different molar ratios. A two-dimensional nonlinear regression analysis of the excess heat capacity surface as a function of temperature and S-peptide concentration enables us to determine the thermodynamic parameters of binding equilibrium. The values obtained are Kb(38.6 °C) ) (1.10 ( 0.15) × 10 6 M-1, ∆bH(38.6 °C) ) (-185 ( 10) kJ mol-1, and ∆bCp ) (-3.5 ( 0.5) kJ K-1 mol-1. These figures result in satisfactory agreement with literature values.