In vivo experiments were conducted with laboratory cultures of toxic Microcystis aeruginosa, to assess the potential impacts of microcystins (MC) on the immune system of the freshwater zebra mussel Dreissena polymorpha.Mussels were fed three toxic cyanobacterial strains, with different toxin profiles (presence of MC-LR and MC-LF) and one nontoxic reference strain, over a 3-wk period. Immunological analyses were carried out with mussels sampled at days 0 (baseline), 7, 14, and 21. A decrease in total hemocyte count was observed at day 14 and thereafter, in mussels exposed to the three MC-containing strains whereas no significant variation in total hemocyte count was observed in mussels exposed to the MC-free cyanobacteria. A short-term increase (at day 7 only) in the granulocyte:hyalinocyte ratio was also observed in mussels exposed to the two most toxic strains and may highlight a potential short-term inflammatory response to MC. Phagocytic rate was significantly lower in mussels exposed to cyanobacteria containing high amounts of MC. The concentration of the defense enzyme, lysozyme, was significantly higher in mussels fed with MC-containing cyanobacteria compared with the control bivalves at day 14 and subsequently increased in a timeand dose-dependent manner. In conclusion, diet exposure toMC appears to have an immunomodulatory effect on zebra mussels, manifested by an initial short-term inflammatory response and followed by the suppression of some of its immune functions. This study, therefore, highlights another potential sublethal effect ofMC on freshwater organisms and illustrates the relative toxicities of the different MC variants, MC-LF being potentially more toxic than MC-LR.