PREDATION can be a potent force structuring ecological communities and affecting several trophic levels1–7. The cascading trophic interactions hypothesis predicts that lacustrine predators such as fish can have a strong effect on herbivorous zooplankton, which in turn can regulate phytoplankton8,9. Ascertaining the scale, scope and generality of this hypothesis is important for both development of ecological theory and aquatic ecosystem management10. Although small-scale tests of parts of this cascade are common11–15, whole-lake assessments are not, particularly in large, natural lakes9; also the influence of several trophic levels and nutrients, a requisite for unambiguous interpretation of predator effects, has not been considered. Here we present data from a natural experiment in Lake Mendota, Wisconsin, USA, which support the cascading trophic interactions hypothesis. Massive mortality of fish greatly reduced prÉdation on zooplankton, resulting in an increase in the abundance of large Daphnia, and a dramatic decrease in phytoplankton biomass. Physical factors and concentrations of limiting nutrients were unchanged before and after fish mortality, indicating that these factors probably did not cause the observed decrease in phytoplankton. Our results demonstrate strong food web influences on phytoplankton, and support the idea that food web interactions can be managed to reduce phytoplankton abundance.