gp96 plays a central role in innate as well as acquired immunity, maturation and chemotaxis of dendritic cells, Ab production, and cross-priming, and is a peptide acceptor in endoplasmic reticulum and an accessory to peptide loading of MHC class I molecules. The remarkable conservation of essential immunological properties of gp96 suggests their important roles during the evolution of the immune system. Considering their importance in immunity, immune evasion mechanisms of pathogens by modulating gp96 expression have been speculated. By differential display PCR, we observed that obligate intracellular bacteria, Orientia tsutsugamushi, inhibit gp96 expression of a macrophage cell line, J774A.1. Not only gp96 transcripts but also protein was lower than for null-infected cells. The down-regulation was also consistent in an endothelial cell line, HMEC-1, and in murine peritoneal cells. These data support the idea that gp96 may be one of the target molecules for the immune evasion by intracellular bacteria.