Gold nanoparticles (AuNPs) are being developed and produced for a wide variety of industrial and biomedical applications, which raises the concern about their release and potential effects in the environment. In this study, we aim to assess the effects of PEGylated AuNPs and ionic gold on the freshwater bivalve Corbicula fluminea. As NP bioavailability is conditioned by many factors of variability, we focused on the determination of biodynamic parameters which control AuNP uptake and elimination in bivalves. Three experiments were conducted: (1) a waterborne exposure (0–24 mg/L for AuNPs and 0–12 mg/L for ionic gold), (2) a dietborne exposure (0–48 mg/L for AuNPs and 0–24 mg/L for ionic gold), and (3) an elimination phase (after waterborne exposure to 12 mg/L for AuNPs and 24 mg/L for ionic gold), to calculate rate constants for uptake from water(kuw), from food (kuf), and for the physiological elimination (ke) for AuNPs and AuCl(OH)3−. Jointly, the relative expression of several genes was investigated in the hemolymph cells to relate AuNPs and gold ion exposures to detoxification, oxidative stress, immune, and apoptosis responses in C. fluminea. Results show that kuw and kuf were around 10 and 30 times higher for AuNPs compared to AuCl(OH)3−, respectively. The ke was also faster in clams exposed to AuNPs meaning that they also had greater excretion capacities in comparison to gold ions. Water seems to be the main exposure pathway for C. fluminea according to kuw and kuf values for AuNPs and AuCl(OH)3− (kuw = 0.28 and 0.03, kuf = 0.009 and 0.001, respectively). The gene analyses pointed out important responses against oxidative stress, strong activations of genes of the immunity, and apoptosis after the waterborne exposure to AuNPs and to a lesser extent after exposure to gold ions. Very few responses were observed after the dietary exposure to both forms of gold, probably due to valve closure in response to contamination. While some studies suggest that the toxicity of nanoparticles may come from the release of metal ions, our results showed that the AuNPs we used were very stable (less than 1% of ion release) and generated more effects at the gene level than ionic gold. Therefore these results highlight the strong potential of toxicity of AuNPs compared to ionic gold and raise new concerns about the toxicity inherent to NPs in the environment.Read less <