The results of fractional factorial experiments showed that the significant external factors affecting high pressure processing (HPP) inactivation were pressure, temperature and pressure holding time. Based on these results, response surface methodology (RSM) was employed in the present work and a second order quadratic equation for HPP inactivation was built. By analyzing the response surface plots and their corresponding contour plots as well as solving the quadratic equation, the experimental values were shown to be in good agreement with predicted values since the correlation coefficient was 0.9891. The optimum process parameters for six log-cycles reduction of Staphylococcus aureus were obtained as: temperature, 34.4 degrees C; pressure, 329.8 MPa and pressure holding time, 15.5 min. The adequacy of the model equation for predicting the optimum response values was verified effectively by the validation data. (c) 2004 Elsevier Ltd. All rights reserved.