Selenium is a trace element characterized by concentrations that narrowly range between being essential and being toxic. Even though inorganic selenite and selenate are the predominantchemicalforms ofSe in surfacewaters, the toxicity of Se to aquatic organisms is mostly governed by the bioavailability of organic selenium within food webs. The present study was designed to evaluate organic selenium bioaccumulation and toxicity patterns in the freshwater sentinel species Corbicula fluminea. Waterborne selenomethionine (SeMet) exposure was used to mimic dietary organo-Se uptake. Our results demonstrate that SeMet is accumulated to a relatively high extentwith a concentration factor of 770 (wet weight basis). Higher uptake than depuration rates suggest that bivalves deal with high Se amounts using a strategy of detoxification based on Se sequestration that could involve granules, as shown by a strong increase of Se in the particulate subcellular fraction. Selenium is persistent in the cytosol of bivalves exposed to SeMet where it is found in proteins of a wide range of molecular mass, indicating a possible replacement of methionine by selenomethionine. A subsequent alteration of protein function might be one of the mechanisms of Se toxicity that could explain the histopathological effects we observed in gills by using transmission electronic microscopy. Those analyses showed changes in gill filament ultrastructure and suggested mitochondria asthefirsttargetfor SeMet cytotoxicity, with alterations of the outer membrane and of cristae morphology. Organo-Se would thus not only be toxic via indirect mechanisms of maternal transfer as it was suggested for fish but also directly. Our results on Se distribution agree with studies that used dietary Se transfer, and highlight the relevance (and less expensive way) of using SeMet water-only exposure protocols to mimic the real environment.