Mussels are quite resistant to cyanotoxins and their resistance may be because of an efficient metabolization of cyanotoxins by glutathione-S-transferases (GST) activity. Nevertheless, other secondary metabolites may interfere with the detoxication efficiency. The accumulation and depuration of hepatotoxins produced by the freshwater cyanobacterium Microcystis aeruginosa in the mussel Mytilus galloprovincialis were studied. Mussels were fed twice a day 1.5x10(5) cells/mL of the toxic cyanobacterium, which produces microcystins (MCs) -FR, -LR and -WR, for 4 days. After that period, the animals were placed in toxin-free water and were fed the green algae Ankistrodesmus sp. During 2 weeks, the concentration of the toxin in the mussels was monitored using an ELISA assay. Mussels showed a maximum detectable level of MCs of 0.38 microg/g mussels dry weight (DW) during the accumulation period and 0.37 microg MC/g mussel DW by day 4 of the depuration period. Then there was a decrease trend with peaks of toxin at days 8 and 12 of the depuration period. The activity of the detoxication enzymes GST was studied and the results showed that the peaks of toxin in the mussels coincide with an increase in the activity of GST. These results support the hypothesis that the rise of the toxin level on days 4, 8 and 12 of the depuration period in the mussels may be related to the renewal of protein phosphatases and subsequent release of unbound toxins.