Glucose regulated protein 75 (GRP75/mortalin/mtHsp70/PBP74/HSPA9B) is a molecular chaperone that was partially cloned and sequenced in gilthead sea bream (Sparus aurata L.) using a RT-PCR and 3'RACE approach. The deduced amino acid sequence supported the early vertebrate divergence of the heat shock protein 70 family into cytoplasmic Hsp70/Hsc70 group, endoplasmic reticulum-resident group and the mitochondrial-type group of GRP75. The tissue-specific regulation of GRP75 was analyzed by real-time PCR and Western blot after acute (24 h, 120 kg/m(3)) and prolonged confinement exposure (3 weeks-trial, 45-50 kg/m(3)). In both experiments, GRP75 gene expression was not significantly altered in brain, head kidney and gills. By contrast, hepatic transcripts of GRP75 were up-regulated and the magnitude of the response was dependent on the intensity of stressor. Furthermore, similar increments in hepatic transcripts and protein levels of GRP75 were found after prolonged confinement exposure. In addition, these stressed animals exhibited a 10% reduction in feed efficiency, significantly increased glycaemia and plasma peroxidases, and their plasma transaminases and respiratory burst of circulating leucocytes were significantly decreased. This stress-mediated response may act in concert with the increased production of hepatic GRP75 to protect metabolically active tissues against oxidative damage.