Determination of the thermodynamic properties of biomolecules at elevated temperatures and pressures is critical to understanding enzymatic activity and the role of hyperthermo-barophilic microbes in both industrial and natural hydrothermal processes. Experimental data reported in the literature indicate that amino acids and other aqueous biomolecules become increasingly sensitive to their chemical environment with increasing temperature. If this environment is not conducive to metastable preservation of biomolecules, they become highly reactive at high temperatures and pressures. However, increasing temperature does not then simply result in decomposition of biomolecules to form H2O, CO2, H-2, and/or other "inorganic" species, but instead they react to form additional "organic" and/or "inorganic" molecules, which may or may not achieve metastable equilibrium with one another under the conditions prevailing in the system. These conditions include the chemical potentials of H-2 (and therefore O-2)(1), CO2, NH3, and H2S. If the chemical potentials of these components are favorable, amino acids and other bimolecules may persist at high temperatures for periods of time well in excess of those required for regeneration of the molecules, either abiotically or by hyperthermobarophilic microbes. Because irreversible reaction of biomolecules with other aqueous species, as well as metastable equilibrium states resulting from such reactions are highly sensitive to the activities of H-2, CO2, NH3, H2S, and other species in solution. these activities must be controlled or at least monitored to achieve unambiguous results in hydrothermal experiments designed to measure the thermodynamic properties of biomolecules as a function of temperature and/or pressure. Such experiments are necessary to calibrate and verify equations of state, which can then be used to characterize the thermodynamic behavior of biomolecules at elevated temperatures and pressures. Only by quantifying this behavior can we determine optimal conditions for enzymatic activity and predict the degree to which reactions among amino acids, polypeptides, proteins, nucleic acids, and other aqueous species are exergonic at high temperatures and pressures. Carefully controlled hydrothermal studies of enzymes and other biomolecules produced by hyperthermobarophilic microbes as a function of temperature, pressure, and the chemical potentials of H-2, CO2, NH3, H2S, and other components of the system should lead to development of new avenues of medical research and a better understanding of bacterial genetics, enzymatic catalysis, DNA replication, and many other biochemical processes on which life depends.