This study investigated whether mercury (Hg) oxidative and genotoxic effects are related with its ability to inhibit selenium-dependent glutathione peroxidase (Se-GPx) activity in haemocytes of mussel Mytilus galloprovincialis. Se-GPx activity was measured both in Se-free cells' cytosolic fraction and in Se-treated cells, pre-treated with 4 microg/l of Se (as sodium selenite), before the exposure to the metal. Hg at concentrations ranged within 10 or 20 microg/l, thus representing the onset of Hg toxic effects, showed to inhibit Se-GPx activity in Se-free cells, followed by increased levels of superoxide anions (()O(2)(-)) and nitric oxide (NO) generation, lipid peroxidation and DNA damage as well. On the other hand, increased enzymatic activity and a significant attenuation of Hg toxicity were measured in Se-treated cells exposed to Hg in all cases. The results of the present study showed that inhibition of Se-GPx activity by Hg could promote a shift in the balance between oxidants and antioxidants in favor of oxidants, resulted in the enhancement of Hg-induced oxidative and genotoxic effects. In addition, Se bioavailability within phagocytic cells, such as haemocytes, could regulate the antioxidant role of Se-GPx, thus reinforcing haemocytes' immune system against toxic effects induced by pro-oxidants, such as Hg.