The stability and the catalytic activity of a carboxypeptidase from the extreme thermophilic archaebacteriaS. solfataricuswas studied over a wide range of temperature (30–95 °C) and pressure (0.1 ‐ 400 MPa), and compared to carboxypeptidase A. The thermostability of both carboxypeptidases could be increased at high pressure. The catalytic activity of the enzyme fromS. solfataricusshowed two temperature dependent domains. Below 60°C, the values of the activation energy and activation volume were large: ?H‡= 44 kJ/mol, ?V‡= 21 ml/mol, suggesting a conformation with a high structural rigidity. In the high temperature domain (above 60 °C), both terms were quite small (?H‡= 9 kJ/mol, ?V‡= 6 ml/mol), comparable to those of carboxypeptidase A which were always small (?H‡= 24 kJ/mol, ?V‡= 0.5 ml/mol), regardless of the temperature. High pressure appeared to shift the enzyme conformation to the properties of the low temperature domain. These results point to the possibility that the thermostability of carboxypeptidase fromS. solfataricusis explained by hydrophobic hydration. This enzyme appears to be an interesting model system for the understanding of the thermo‐ and barostability of proteases.