The strategies used by bacterial pathogens to circumvent host defense mechanisms remain largely undefined in bivalve molluscs. In this study, we investigated experimentally the interactions between the Pacific oyster (Crassostrea gigas) immune system and Vibrio aestuarianus strain 01/32, a pathogenic bacterium originally isolated from moribund oysters. First, an antibiotic-resistant V. aestuarianus strain was used to demonstrate that only a limited number of bacterial cells was detected in the host circulatory system, suggesting that the bacteria may localize in some organs. Second, we examined the host defense responses to V. aestuarianus at the cellular and molecular levels, using flow-cytometry and real-time PCR techniques. We showed that hemocyte phagocytosis and adhesive capabilities were affected during the course of infection. Our results also uncovered a previously-undescribed mechanism used by a Vibrio in the initial stages of host interaction: deregulation of the hemocyte oxidative metabolism by enhancing the production of reactive oxygen species and down-regulating superoxide dismutase (Cg-EcSOD) gene expression. This deregulation may provide an opportunity to the pathogen by impairing hemocyte functions and survival. These findings provide new insights into the cellular and molecular bases of the host-pathogen interactions in C. gigas oyster. (c) 2006 Elsevier Masson SAS. All rights reserved.