Antioxidant response was used to assess the effects of the main pollutants in wild mussels (Mytilus galloprovincialis) along the Mediterranean coast of Spain. Antioxidant enzyme activities - those of catalase, superoxide dismutase, glutathione peroxidases, glutathione reductase, glutathione S-transferase and DT-diaphorase - as well as lipid peroxidation and metallothionein concentrations were measured in gills of mussels from 16 selected sites. Furthermore, concentrations of the main contaminants (Hg, Pb, Cd, Cu, Zn, As, PAH, PCB, and DDT) were quantified in mussel tissue, and environmental parameters were measured in water samples collected at each site. Results showed that the glutathione-dependent antioxidant enzymes offered an increased and coordinated response against metal (Hg, Pb and Cd) contamination. These enzymatic activities correlated positively to temperature, suggesting the influence of this environmental parameter on antioxidant responses in gill tissues. Furthermore, although temperature did not reach stressful levels in the study area, it seemed to add a synergistic effect to that produced by metals to induce antioxidant enzymes in the most metal-polluted sites. Catalase activity appeared to be involved in a different antioxidant pathway, more related to organic pollutant bioaccumulation, offering an efficient protection mechanism against reactive oxygen species generation due both to organic exposure and high physiological activity, reflected by high condition indices. In general terms, increased levels of antioxidant enzymes at some sites suffering from metal and organic pollution indicated a situation of oxidative stress that nevertheless did not appear to be harmful, since lipid peroxidation levels showed no peroxidative damage in gill tissues of mussels collected from even the most heavily polluted sites. On the other hand, metallothionein and DT-diaphorase did not reflect pollutant exposure and seemed to be more influenced by environmental variables than by the pollutants.