Cadmium and zinc uptake from the dissolved phase, assimilation efficiency from the dietary phase, efflux rate constants, and body burden as well as clearance rate were measured in the green mussel Perna viridis with or without laboratory preexposure to Cd or Zn. Efflux rate constants and clearance rates were little affected by preexposure to either Cd or Zn. In contrast, the assimilation of Cd increased by 1.2-1.6x in mussels preexposed to Cd (subsequent Cd concentrations 10.2-25.9 μg g-1) as compared to controls (0.19-0.39 μg g-1). This increase corresponded to an elevation in the proportion of Cd associated with the metallothionein-like proteins (MTLPs) in the mussels, suggesting that exposure to Cd and subsequent induction of MTLPs affected Cd accumulation. Exposure to Zn only resulted in elevated body concentrations following 7-d exposure to 250 μg L-1, although Zn and Cd uptake from the dissolved phase were reduced by 24-47% by exposure to a lower concentration (100 μg L-1) for 7 and 21 d. Despite the lack of an increase in body Zn concentration, the subcellular distribution was altered such that the proportion of Zn associated with the metal-rich granules increased. This study indicates the importance of the subcellular distribution of metals in affecting the biokinetics and thus the toxic effects of metals on aquatic animals. Cd preexposure has potential effects on its influx from the dietary phase, e.g., increasing the importance of dietary uptake and further increasing the body burdens. In contrast, preexposure to Zn has a negative effect on Cd and Zn influx from the dissolved phase, suggesting the mechanism of Zn regulation but also potentially reducing Cd uptake and body concentrations over the long-term exposure. Such effects may have implications for biomonitoring studies involving a single species that modifies physiological processes affecting metal uptake (and hence bioavailability). Caution is needed in extrapolating data to species not capable of making such changes, particularly for Cd, which is not regulated and for which the effects of an elevated body burden are most obvious.