The aim of this study was to investigate the natural role of the mantle in pearl oyster, Pinctada fucata. The mantle is believed to be the tissue responsible for shell and pearl formation. However, our current study on lead and copper accumulation in tissues of the oyster showed that the secondary tissue for lead accumulation was not the digestive gland but the mantle. In view of high lead concentrations in the mantle, its general metabolic condition (including immune and antioxidant defense systems) as affected by the two metals was studied. The results indicated that activities of antioxidant enzymes (superoxide dismutase, SOD; Se-dependent glutathione peroxidase, Se-GPx) were altered by lead and copper in the similar way. However, the immune enzyme activities (acid phosphatase, AcPase; phenoloxidase, PO) were perturbed differently by two metals. Therefore, the mantle of P. fucata was predicted to participate in immune processes and accumulation or detoxification of lead besides shell formation. Our observations described here may also provide important clues to further understanding of the biomarker responses of bivalves. © 2007 Elsevier B.V. All rights reserved.