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Oysters ( Crassostrea gigas ) farmed in a clean reference estuary were exposed to different combinations of 63 Cu and 107 Ag stable isotope spikes in seawater at environmentally relevant concentrations during 28 days in order to study short-term bioaccumulation kinetics. Oysters were sampled, dissected and analyzed for Cu and Ag concentrations and isotope ratios ( 63/65 Cu; 107/109 Ag) after 7, 14, 21 and 28 days of exposure. Isotope ratios in oyster tissues showed significant differences from natural isotope ratios even after only 7 days of exposure, with relatively similar signals independent from the tissue. The changes in isotope ratios combined with conventional concentration measurements allowed precise quantification of 63 Cu and 107 Ag concentrations before experimental exposure, in the same individual oyster tissue. The high sensitivity and the possibility to precisely follow short-term accumulation at environmental levels of several (non radioactive) different metals in individual organisms are major advantages. Relatively constant Cu/Ag ratios in oysters exposed to the lowest Cu and Ag concentrations were observed. However, interactions between Cu and Ag accumulation occurred with (i) a synergy effect increasing Ag accumulation in the presence of high Cu concentrations and (ii) antagonism resulting in lower Cu accumulation at a given Cu exposure when Ag exposure levels increase. Comparison of experimentally accumulated Cu/Ag ratios ( 63 Cu acc / 107 Ag acc ) with Cu/Ag in wildlife oysters along the French Atlantic coast (data provided by the national mussel watch program RNO/ROCCH) suggests that such metal ratios reflect, to a certain extent, exposure levels and proportions in the environment. As such, element ratios may indicate contamination sources better than metal concentrations alone. Metal accumulation in the different oyster tissues (mantle, muscle, gills, digestive gland and gonads) was rather homogeneous during the short-term direct exposure experiment, whereas wild oysters from the Gironde Estuary show very strong differences in metal accumulation between tissues, i.e. maximum Ag accumulation in digestive gland. This suggests that the trophic pathway (metals contaminating oysters through the food intake) may play a major role in wildlife oyster contamination. [ABSTRACT FROM AUTHOR]