The cyanotoxin cylindrospermopsin (CYN) is produced by several species of cyanobacteria and can be persistent in drinking waters supplies, which is of major concern to water authorities because of its potential to severely compromise human health. Consequently, there is a need to fully understand the persistence of CYN in water supplies, in particular, to determine whether this toxin is readily degraded by endemic aquatic organisms. This study provides insights into the environmental factors that can influence the biodegradation of this toxin in Australian drinking water supplies. Biodegradation of CYN was only evident in water supplies that had a history of toxic Cylindrospermopsis raciborskii blooms. In addition, lag periods were evident prior to the onset of biodegradation; however, repeated exposure of the endemic organisms to CYN resulted in substantial decreases in the lag periods. Furthermore, the concentration of CYN was shown to influence biodegradation with a near linear relationship (R2 of 0.9549) existing between the biodegradation rate and the initial CYN concentration. Temperature was also shown to affect the biodegradation of CYN, which is important since CYN is now being detected in more temperate climates. The presence of copper-based algicides inhibited CYN degradation, which has significant implications since copper-based algicides are commonly used to control cyanobacterial growth in water bodies. The results from this study indicate that the biodegradation of CYN in natural water bodies is a complex process that can be influenced by many environmental factors, some of which include CYN concentration, temperature, and the presence of copper-based algicides. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008.