A large scale study of trace metal contamination (Hg, Cd, Pb and Ni) by means of caged mussels Mytilus galloprovincialis was undertaken along the coastal waters of the Western Mediterranean Sea within the context of the MYTILOS project. Individual mussels from an homogeneous population (shell size 50 +/- 5 mm) obtained from an aquaculture farm were consecutively caged and deployed at 123 sites located in the Alboran, North-Western, South-Western and Tyrrhenian sub-basins for 12 weeks (April-July) in 2004, 2005 and 2006. After cage recoveries, both the metal content in the whole mussel tissue and the allometric parameters were measured. Statistical analysis of the datasets showed significant differences in concentrations between sub-basins for some metals and mussel condition index (CI). Linear regression models coupled to the CI were revisited for the data adjustment of certain trace metals (Hg, Cd and Ni), and four level categories were statistically derived to facilitate interregional comparison. Seawater masses surrounding coastal areas impacted by run-off from land mineralised coasts and industrial activities displayed the highest concentration ranges (Hg: 0.15-0.31 mg kg(-1) dw; Cd: 1.97-2.11; Ni: 2.18-3.20 and Pb: 3.1-3.8), although the levels obtained in most of the sites fitted within moderate or low categories, and they could be considered as baseline concentrations. However, few sites considered little-influenced by human activities, at present, showed high concentrations of Cd, Ni and Pb, which constitute new areas of concern. Overall, the use of active biomonitoring (ABM) approach allowed to investigate trace metal contamination in order to support policy makers in establishing regional strategies (particularly, with regard to the European Marine Strategy Directive).