Although it is often assumed that the pH of a buffer solution remains constant during a differential scanning calorimetry (DSC) experiment, the pK of a buffer can in fact change signifi cantly between 0 ^oC and 100 ^oC. Such pH changes can result in sample denaturation, aggregation and precipitation that, in the absence of knowledge about the temperature stability of the buffer, could erroneously be ascribed solely to temperature-induced unfolding of the biomolecule.