The thermal denaturation of azurin from Pseudomonas aeruginosa was investigated by means of differential scanning calorimetry (DSC), electron spin resonance (ESR), and optical density (OD) experiments, with the aim of determining its thermodynamic stability and the thermally induced conformational changes of its active site. DSC experiments have shown an irreversible and complex unfolding path. In order to characterize the kinetically controlled step, DSC measurements were carried out at different scan rates. An extrapolation of the experimental heat capacity data to infinite scan rate allowed all the kinetic and thermodynamic parameters related to the process to be obtained. All these parameters extracted from the calorimetric data were verified by means of a curve-fitting program using an equation containing all information necessary to fully describe the unfolding process in details. Thermal denaturation, followed up to 82 degrees C by ESR and OD measurements, allowed us to study the structural variations of the copper environment at different temperatures. The Delta H-U thermodynamic, together with the value of Delta C-p calculated according to an approach taking into account the common features of protein unfolding and dissolution of hydrophobic compounds, was used to evaluate the thermodynamic stability (Delta G) for the reversible process over the entire temperature range of denaturation. The high value of the maximum stability thus calculated was explained by the stabilizing effect of copper.