In bivalve molluscs the digestive gland (hepatopancreas) plays a central role in metabolism. In this work, the effects of 17beta-estradiol (E(2)) on digestive gland were evaluated in Mytilus galloprovincialis. Mussels were injected into the adductor muscle sinus with different amounts of the hormone (5, 25 and 100pmol) and tissues were sampled 24h post-injection. Functional parameters (lysosomal membrane stability-LMS, lysosomal accumulation of neutral lipids-NL and of lipofuscin-LF), as well as the activity of the key glycolytic enzymes PFK (phosphofructokinase) and PK (pyruvate kinase), and of the antioxidant enzyme catalase were evaluated. Selected genes, whose expression can be modulated by estrogens in mammalian systems and whose sequences have been identified in Mytilus, were investigated as possible targets for the action of E(2). E(2) induced a concentration-dependent decrease in LMS; such an effect was accompanied by an increase in NL accumulation, whereas the level of lipofuscin showed a slight, although not significant decrease. E(2) exposure also led to a significant increase in the activity of PFK and catalase but not of PK. Moreover, E(2) induced significant changes in the pattern of gene expression at the lower concentrations tested (5 and 25pmol) as evaluated by quantitative RT-PCR. In particular, increased transcription of catalase, as well as of the metallothionein 20 (MT20) isoform were observed; on the other hand, a decreased transcription of the p53 gene was detected. The results demonstrate that in Mytilus the digestive gland represents a target for the action of E(2), and that the hormone can modulate the lysosomal function, as well as lipid and glucose metabolism. Moreover, these data suggest that E(2) may also alter oxidative stress conditions in this tissue, as indicated by the increased transcription of genes (metallothionein and catalase) that play a role in antioxidant defences. Overall, the results indicate that E(2) can modulate both functional parameters and gene expression in mussel hepatopancreas and underline the importance of investigating also non-reproductive effects of estrogenic compounds in bivalve molluscs.