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A comparative of the species composition and ecological-geographical characteristics of cyanobacteria plankton of 13 reservoirs of the Volga-Kama cascade and the Don (Sheksna, Ivankovo, Uglich, Rybinsk, Gorky, Cheboksary, Kuibyshev, Saratov, Volgograd, Kama, Votkinsk, Nizhnekamsk and Tsimlyansk reservoirs) is analysed. An assessment of the change in the distribution of cyanobacteria biomass in a latitudinal gradient along the Volga cascade is presented. The seasonal and long-term (1954–2016) dynamics of the abundance, biomass and the ratio of functional groups of cyanobacteria in the Rybinsk Reservoir, the second largest in the cascade of Volga reservoirs, are analyzed. A positive long-term trend of abundance and diversity of cyanobacteria and the leveling of their biomass between reservoirs along a cascade in recent years has been established. An increase in the abundance and diversity of nonheterocystous species was established in the direction from the Upper to the Lower Volga and during the long-term succession of phytoplankton of the Rybinsk Reservoir. This is associated with an increase of water mineralization. Based on current research in the 2010s of the Volga, Kama and Don cascade reservoirs, 14 variants of microcystin structures were identified, the diversity of which depended on the composition of the producing species. Using PCR analysis, the main producers of microcystins (Microcystis and Dolichospermum) were identified. Cyanobacteria Cuspidothrix issatschenkoi and/or Raphidiopsis mediterranea have been identified as possible producers of neurotoxic anatoxin-a in the Tsimlyansk Reservoir. It was shown that water temperature and nitrogen were the greatest importance for development of microcystin-producing species of cyanobacteria.