Ag and CuO engineered nanoparticles (ENPs) have wide applications in industry and commercial products and may be released from wastewater into the aquatic environment. Limited information is currently available on metal ENP effects, uptake, and depuration kinetics in aquatic organisms. In the present study, a deposit-feeding clam, Macoma balthica, was exposed to sediment spiked with Ag and Cu in different forms (aqueous ions, nanoparticles, and micrometer-sized particles) in three experiments. In all experiments, no effects on mortality, condition index, or burrowing behavior were observed for any of the metal forms at measured sediment concentrations (150−200 μg/g) during 35 d of exposure. No genotoxicity was observed following exposure, measured as DNA damage with the single-cell gel electrophoresis assay (comet assay). Bioaccumulation of both Ag and Cu in the clams was form dependent such that bioaccumulation from sediment spiked with aqueous ions > nanoparticles > micrometer-sized particles. Cu uptake and depuration kinetics were studied in more detail yielding net uptake rates (μg Cu/g dw soft tissue/d) in soft tissue of 0.640, 0.464, and 0.091 for sediment spiked with aqueous Cu ions, CuO nanoparticle,s and micrometer-sized CuO particles, respectively, supporting that net uptake was dependent on form. Depuration rate constants (d−1) from soft tissue were −0.074, −0.030, and 0.019 for Cu added to sediment as aqueous Cu ions, CuO
nanoparticles, and micrometer-sized CuO particles, respectively. Ensuring sustainable use of nanotechnology requires the development of better methods for detecting and quantifying ENPs, particularly in sediment.