In the North-Cotentin (Normandy, France), the marine environment is chronically exposed to liquid releases from the La Hague nuclear fuel recycling plant (Areva NC), resulting in a small increase in radioactivity compared to natural background. The transcriptional expression levels of stress genes were investigated in oysters exposed to ionizing radiation. Adult oysters were kept for 6 weeks in ⁶⁰Co-labeled seawater (400 Bq liter⁻¹), resulting in a total dose of 6.2 mGy. Transcriptional expression of target genes was monitored by reverse-transcription quantitative polymerase chain reaction. Nine genes were selected for their sensitivity to ionizing radiation based on the literature and available DNA sequences. They included genes encoding chaperone proteins and genes involved in oxidative stress regulation, cell detoxification and cell cycle regulation. Of the nine genes of interest, metallothionein (MT) and multi-drug resistance (MDR) displayed significant overexpression in response to chronic exposure to an internal low dose. For comparison, oysters were acutely exposed to an external high dose for 100 min, resulting in 20 Gy, and the same target gene expression analysis was carried out. As in the case of chronic exposure to the low dose, MT and MDR displayed significant increases. The results suggest that the transcriptional expression levels of cell stress genes may be used as a biosensor of exposure of oysters to ionizing radiation, with a particular focus on the MT and MDR genes. However, the upregulation of these potential players in the cellular response to radiation-induced stress was not correlated with mortality or apparent morbidity. The possible role of these stress genes in the resistance of oysters to ionizing radiation is discussed.