The importance of understanding the mechanisms underlying insecticide disturbances in natural systems is growing because of increasing global insecticide use. Despite the prevalence of pesticides and the vulnerability of aquatic systems to insecticides, little is understood about the effect of lower concentrations of insecticides (<1 ppm) on aquatic community interactions. Whether insecticide effects are generalizable across different aquatic assemblages and trophic levels also is unclear. Furthermore, few investigators have examined the indirect consequences of insecticides beyond the primary consumer level. We examined how a single application of malathion at 3 concentrations (0, 6, or 40 µg/L) and the presence or absence of zooplankton predators (larval salamanders) affected aquatic communities composed of zooplankton, phytoplankton, periphyton, and 2 geographically distinct amphibian assemblages from Oregon and Pennsylvania. At these concentrations, malathion was directly lethal to certain zooplankton species, causing a shift from cladoceran-dominated assemblages to copepod-dominated assemblages. The decrease in cladoceran abundance released top-down pressure on phytoplankton, allowing an increase in phytoplankton abundance. The increase in phytoplankton was associated with a decrease in periphyton (the major food source of anurans) because of competition between phytoplankton and periphyton. We did not find direct mortality in anurans or salamanders, but the insecticide-mediated reduction in zooplankton indirectly caused a decrease in larval salamander mass. In contrast, anurans exposed to malathion were heavier at metamorphosis. Overall, these results demonstrate that low concentrations of insecticides have indirect consequences on nontarget members of the community across multiple trophic levels, and the indirect insecticide-mediated effects are generalizable across 2 geographically distinct amphibian assemblages.