Differential scanning calorimetry (DSC) was used to evaluate the relative high hydrostatic pressure (HHP) resistances of bacterial strains from Staphylococcus aureus and Escherichia coli O157:H7 in vivo. The total apparent enthalpy change and thermal stability were two DSC parameters used to compare bacterial strains of untreated control and pressure-treated bacteria. DSC thermograms indicated that ribosomal denaturation appears to be a major factor in cell death by both thermal and high pressure treatments. However, the analysis of calorimetric data for control samples as well as pressure-treated samples clearly showed that the sensitivities of bacteria to various physical stresses can be different. While S. aureus 765 had a relatively higher resistance to thermal treatment in comparison to S. aureus 485, S. aureus 485 was determined to be more resistant to pressure than S. aureus 765. This information can be utilized in the design of processes specific to targeting certain cellular components by using different physical stresses.