The composition of near shore marine environments is increasingly being altered by contaminants from human activities. The ability of lead, which has no known biological function, to mimic biologically essential metals makes it one of the most toxic to marine biota. The relationship between lead exposure, dose and response was investigated in Anadara trapezia exposed for 56 days to lead spiked sediment (100 and 300 g/g dry mass). Lead tissue concentrations of the 300 g/g exposed A. trapezia doubled in the last 2 weeks of exposure with final lead tissue concentrations of exposed organisms of 1 and 12 g/g, respectively. Tissue lead accumulation of exposed organisms followed the pattern haemolymph > gill > hepatopancreas during much of the 56 day exposure. Between 30 and 69% of accumulated lead in the gill and hepatopancreas was detoxified and fairly evenly distributed between the metal rich granule and the metallothionein like protein fractions. Approximately half of the biologically active lead in both tissues was in the mitochondrial fraction which showed increased cytochrome c oxidase activity in lead exposed organisms. There was a reduction in GPx activity, an associated increase in total glutathione concentrations and reduced GSH:GSSG ratios due to a build up of oxidised glutathione. These changes in the glutathione pathway were reflected in the total antioxidant capacity of lead exposed A. trapezia which were significantly reduced compared to control organisms. Increased lead exposure significantly increased lipid peroxidation, lysosomal destabilisation and frequency of micronuclei. A significant exposureâ¿¿doseâ¿¿response relationship for A. trapezia exposed to lead enriched sediments indicates that elevated sediment lead concentrations have the potential to increase biologically active lead burdens and impair the antioxidant reduction capacity leading to a series of associated effects from lipid peroxidation to cellular perturbation and genotoxic damage.