White spot syndrome virus (WSSV), the etiologic agent of white spot disease, is currently the most important viral pathogen infecting penaeid shrimp worldwide. Since the initial report, white spot disease has caused losses of catastrophic proportion to shrimp aquaculture globally. Although considerable progress has been made in characterizing the WSSV and developing detection methods, information on the host genes involved in the immune response in shrimp due to WSSV infection is not available. During this research, the mRNA expression profiles in healthy and WSSV-infected shrimp were determined by analyzing the expressed sequence tags (ESTs) and by microarray analysis. Our data show that WSSV infection alters the expression of a wide array of genes including those that are involved in immune function, signal transduction, structural genes, as well as mitochondrial genes among others. Using EST analysis and real-time RT-PCR, we also identified a candidate receptor gene for another viral pathogen of shrimp, the Taura syndrome virus (TSV). These data show that the potential for using the mRNA expression level of candidate genes as biomarkers for identifying virus-resistant or virus-susceptible lines in shrimp.