The biological interactions and the physical and chemical properties of the littoral zone of Lake Krugersdrift were studied for a 4-month period when a dense, toxic cyanobacterial bloom dominated by Microcystis aeruginosa was present in the main lake basin. The presence of a toxic strain of M. aeruginosa was confirmed through the use of ELISA and molecular markers that detect the presence of the mcyB and mcyD genes of the mcy gene cluster that synthesizes microcystin. An increase in Microcystis toxicity at sites dominated by the cyanobacterial scum was accompanied by an increase in total abundance of the macroinvertebrate families Hirudinae, Chironomidae, and Tubificidae. Sites located away from the cyanobacterial scum had a lower abundance but a higher diversity of macroinvertebrates. The water quality under the Microcystis scum was characterized by low pH values, low concentrations of dissolved oxygen, and lower total alkalinity values. The periphytic alga Ulothrix zonata was absent in areas dominated by the cyanobacterial scum, possibly as a result of overshadowing by the scum or direct toxic allelopathic effects on growth and photosynthesis. The diatom Diatoma vulgare dominated the benthic algal flora beneath the cyanobacterial scum.