The role of subcellular partitioning of copper on the sublethal effects to two deposit-feeding organisms (41-day growth in the bivalve Tellina deltoidalis and 11-day reproduction in the amphipod Melita plumulosa) was assessed for copper-spiked sediments with different geochemical properties. Large differences in bioaccumulation and detoxification strategies were observed. The bivalve accumulated copper faster than the amphipod, and can be considered a relatively strong net bioaccumulator. The bivalve, however, appears to regulate the metabolically available fraction (MAF) of the total metal pool by increasing the net accumulation rate of copper in the biologically detoxified metal pool (BDM), where most of the copper is stored. In the amphipod, BDM concentration remained constant with increasing copper exposures and it can be considered a very weak net bioaccumulator of copper. This regulation of copper, with relatively little stored in detoxified forms, appears to best describe the strategy applied by the amphipod to minimize the potential toxic effects of copper. When the EC50 values for growth and reproduction are expressed based on the MAF of copper, the sensitivity of the two species appears similar, however when expressed based on the net accumulation rate of copper in the metabolically available fraction (MAFrate), the bivalve appears more sensitive to copper. These results indicate that describing the causality of metal effects in terms of kinetics of uptake, detoxification, and excretion rather than threshold metal body concentrations is more effective in predicting the toxic effects of copper. Although the expression of metal toxicity in terms of the rate at which the metal is bioaccumulated into metabolically available forms may not be feasible for routine assessments, a deeper understanding of uptake rates from all exposure routes may improve our ability to assess the risk posed by metal-contaminated sediments.