High hydrostatic pressure processing (HPP) is currently being used as a treatment for certain foods to control the presence of food-borne pathogens, such as Listeria monocytogenes. Genomic microarray analysis was performed to determine the effects of HPP on L. monocytogenes in order to understand how it responds to mechanical stress injury. Reverse transcriptase PCR analysis of tufA and rpoC indicated that the reduction of mRNA expression in HPP-treated cells was dependent on intensity and time of the treatment. Treatments of 400 and 600 MPa for 5 min on cells in the exponential growth phase, though leading to partial or complete cellular inactivation, still resulted in measurable relative differential gene expression. Gene set enrichment analysis indicated that HPP induced increased expression of genes associated with DNA repair mechanisms, transcription and translation protein complexes, the septal ring, the general protein translocase system, flagella assemblage and chemotaxis, and lipid and peptidoglycan biosynthetic pathways. On the other hand, HPP appears to suppress a wide range of energy production and conversion, carbohydrate metabolism and virulence-associated genes accompanied by strong suppression of the SigB and PrfA regulons. HPP also affected genes controlled by the pleotrophic regulator CodY. HPP-induced cellular damage appears to lead to increased expression of genes linked to sections of the cell previously shown in bacteria to be damaged or altered during HPP exposure and suppression of gene expression associated with cellular growth processes and virulence.Listeria monocytogenes is a Gram-positive, non-sporulating, rod-shaped, facultative anaerobe that is a member of the phylum Firmicutes and causes the disease listeriosis. Listeriosis is an uncommon but very serious condition that has a high mortality rate amongst susceptible individuals and is acquired orally through the consumption of food (Khelef et al., 2006). Due to its environmentally robust and persistent nature, the control and elimination of L. monocytogenes currently remains a challenge and a priority for the food industry (Bell & Kyriakides, 2005), especially considering the increasing consumer demand for convenience foods that often have varied and minimal conventional post-lethality processing treatments. This concern has led to various technologydriven innovations in food processing, including the application of thermal and non-thermal high hydrostatic pressure processing (HPP) to inactivate and kill pathogenic bacteria present in food or in raw ingredients (Toepfl et al., 2006). High pressure damages cellular membranes, resulting in leakage of cell contents; oligomeric proteins and protein complexes also undergo dissociation (Gross & Jaenicke, 1994). In combination these cellular injuries lead to cell inactivation and death. Protein and nucleic acid complexes in the cell with critical functions, e.g. ribosomes and the translation apparatus (Niven et al., 1999) and septal rings (Kawarai et al., 2004) are particularly vulnerable...