Circular dichroism spectroscopy was used to measure the thermal unfolding of bovine pancreatic ribonuclease A (RNase A) with various concentrations of guanidine hydrochloride (GuHCl). A red shift in transition midpoint temperatures, T[subscript m], occurred with increasing concentration of the strong protein denaturant. van Hoff enthalpy changes, [delta]H[degree], were calculated and plotted as a function of T[subscript m] to determine the heat capacity change, [delta]C[subscript p], for denaturation. A value of 4.02 plus or minus 0.02 kJ mol[superscript -1] K[superscript -1] was calculated from d([delta]H)/d([delta]T[subscript m]). Reported values for [delta]C[subscript p] range from 4.2 to 9.6 kJ mol[superscript -1] K[superscript -1]. The shift in T[subscript m] for RNase A with increasing concentration of GuHCl suggests that the protein is undergoing substantial changes in its secondary structure.(Contains 6 figures and 1 table.)