We aimed to determine the effects of linear cyanobacterial oligopeptides: microginin-FR1 (MG-FR1), anabaenopeptin-B (ANA-B), aeruginosin 98A (AER-A), aeruginosin 98B (AER-B) and their binary and quaternary mixtures on RTgill-W1 cell line. The following cellular parameters were determined after 48-h exposure: propapoptotic caspase 3/7, heat shock protein 70 kDa (HSP70) level, cAMP level as an indicator of interaction with G protein-coupled receptors (GPCRs) and tyrosine phosphatase level. The study showed that caspase 3/7 level was increased in cells exposed to the tested single (MG-FR1 was the most potent stimulator) and mixtures of the oligopeptides (the most potent was ANA-B + AER-A), mostly with synergistic interactions. Single MG-FR1, AER-A, AER-B and AER-B increased the level of HSP70 The highest augmentation was noted in cells exposed to AER-A and AER-B. On the other hand, ANA-B and the mixture of MG-FR1+ANA-B induced a concentration-dependent inhibition but the other binary mixtures increased this parameter. The quaternary mixture was the most effective stimulator of HSP70 production. Both single cyanobacterial metabolites and their mixtures decreased the level of cAMP at the highest concentrations. The single tested oligopeptides and their mixtures had poor effects on tyrosine phosphatases. Only ANA-B and the binary mixture of MG-FR1+ANA-B reduced this parameter. The results show that cyanobacterial oligopeptides should be considered as stressful agents to fish gills and may contribute to various biochemical alterations and physiological disorders in these aquatic vertebrates