ABSTRACT: Establishment of a high-pressure sterilization process requires data on pressure and temperature-dependent inactivation kinetics of target pathogenic, spoilage, or surrogate spore-forming bacteria in the food being tested. The objective of this study was to examine the response of Geobacillus stearothermophilus ATCC10149 spores to various temperature, time, and pressure combination treatments (500 to 700 MPa; 92°C to 111°C, 0.01 to 360 s). The pressure inactivation of spores was characterized at elevated temperatures under isobaric and isothermal conditions during the holding time using a laboratory-scale high-pressure unit. The inactivation kinetics was well described by the log-linear regression model. As expected, the rate of spore inactivation increased with increasing pressure and temperature. Decimal reduction times at constant pressure (DT,P values) varied from 29.4 to 108.8 s at 92°C, 17.4 to 76 s at 100°C, and 6.1 to 51.3 s at 111°C within the pressure range of 500 to 700 MPa. The resistance of spores to temperature and pressure was characterized with zT and zP values and compared with their resistance to conventional steam heating. The conventional thermal resistance of G. stearothermophilus species did not correlate to the thermal resistance at high pressure. The study provides kinetic data on the effects of pressure and temperature on the inactivation of a heat-resistant bacterial spore species under conditions applicable to the commercial processing of low-acid foods.