Marine intertidal organisms commonly face hypoxic stress during low tide emersion; moreover, eutrophic conditions and sediment nearness could lead to hypoxic phenomena; it is indeed important to understand the molecular processes involved in the response to hypoxia. In this study the molecular response of the Pacific oyster Crassostrea gigas to prolonged hypoxia (2 mg O-2 L-1 for 20 d) was investigated under experimental conditions. A transcriptomic approach was employed using a cDNA microarray of 9058 C. gigas clones to highlight the genetic expression patterns of the Pacific oyster under hypoxic conditions. Lines of oysters resistant (R) and susceptible (S) to summer mortality were used in this study. ANOVA analysis was used to identify the genes involved in the response to hypoxia in comparison to normoxic conditions. The hypoxic response was maximal at day 20. The principal biological processes up-regulated by hypoxic stress were antioxidant defense and the respiratory chain compartment, suggesting oxidative stress caused by hypoxia or an anticipatory response for normoxic recovery. This is the first study employing microarrays to characterize the genetic markers and metabolic pathways responding to hypoxic stress in C gigas. (C) 2010 Elsevier B.V. All rights reserved.