Microcystins (MC) produced by several cyanobacteria are potent hepatotoxins, whereas the toxicokinetics and subsequent detrimental effects ofMCare not fully understood in marine bivalves. In this study, the accumulation and depuration pattern of MC-Leucine-Arginine (MC-LR) along with the antioxidant response were investigated in the gill tissue of Pacific oyster Crassostrea gigas and blue mussel Mytilus edulis exposed to 0.1, 1, 10, and 20 µg L-1 MC-LR for 7 days. Time- and concentration-dependent accumulation and depuration of MC-LR were observed in the gill tissue during the exposure and depuration phases. The values for maximum accumulation of MC-LR and malondialdehyde content were statistically significant (P < 0.05) at the end of exposure (day 7) to 20 µg L-1 MC-LR for both the bivalves, and at the beginning of the depuration period when M. edulis and C. gigas were exposed to 10 and 20 µg L-1, respectively. A significant level of glutathione (GSH) was detected in M. edulis in response to 20 µg L-1 MC-LR during the exposure and depuration periods, whereas no significant levels of GSH were detected in C. gigas. The MC-LR accumulation induced oxidative stress in the gill tissue through modulation of the activities of antioxidant enzymes, the antioxidant response being more significant in the mussel than in the oyster. The enzymatic activities of glutathione S-transferase, superoxide dismutase (SOD), glutathione peroxidase, and glutathione reductase (GR) increased significantly in M. edulis, whereas in C. gigas, significant increase in the activities of SOD, catalase, and GR were observed at the end of exposure (day 7) to 20 µg L-1 MC-LR. Similarly, during the depuration period, significant increases in the antioxidant activities were observed in M. edulis mostly at the beginning (day 1 and day 5) of exposure compared with the levels in C. gigas. The results obtained in this study will be useful in the understanding of MC-LR accumulation in bivalve gill tissues and the subsequent antioxidant defense response.