Cyanobacterial toxins, especially microcystins (MC), are found in eutrophied waters through the world. Acute poisonings of animals and humans has been reported following MC exposure. In the present study, two fish cell lines, PLHC-1 and RTG-2, were evaluated after exposure to the cyanobacterial toxins MC-LR and MC-RR. The effects of different concentrations of the toxins were investigated in both cell lines at morphological and biochemical levels (total protein content, lactate dehydrogenase leakage, lysosomal activity and succinate dehydrogenase activity). The results obtained showed a decrease in protein content and no relevant increase in cell disruption, except for MC-LR in PLHC-1 cells. Morphological changes produced by microcystins were cellular swelling, blebbling, rounding, reduction in the cell number and increase in the number and size of lysosomal bodies. In addition, steatosis was produced in hepatoma PLHC-1 cells, particularly with MC-RR. Furthermore, the fish PLHC-1 cell line was more sensitive than RTG-2 cells to the cyanobacterial toxins compared, being the stimulation of the lysosomal function and the induction of steatosis the most specific changes detected.