In this study the clam, Tapes philippinarum, a filter-feeding bivalve living in soft bottoms, was used to investigate the water/sediment pollution in Venice Lagoon (Venice, Italy), a heavily urbanised and industrialised area. To this end, clams collected from indigenous populations in a clean farming area (Val Dogà) were transplanted into a relatively low contaminated site (Palude della Rosa) and in a heavily polluted area (Porto Marghera), for 5 weeks. A range of possible induced stress indices were measured, on the basis of potential toxicity mechanisms, including specific enzymatic activities [Bap hydroxylase and NADPH cytochrome c reductase, superoxide dismutase, catalase, glutathione peroxidase and propionaldehyde dehydrogenase (PDH)] and general cellular responses (lysosomal latency). Moreover, chemical analyses (polychlorinated biphenyls, polycyclic aromatic hydrocarbon, DDTs) were carried out on sediments and animal tissues at the beginning and end of the transplantation experiments. The chemical results show an active bio-accumulation activity from sediment in clams translocated to the most polluted area. Correspondingly, biological data indicate marked effects on PDH activity and latency in T. philippinarum from the same site. In contrast, no similar pattern has been observed in the other considered indices, possibly due to antagonistic effects of the complex contaminant mixture present in the environment.