To understand the potential effects of pesticide mixtures on aquatic ecosystems, studies that incorporate increased ecological relevance are crucial. Using outdoor mesocosms, the authors examined long-term effects on aquatic invertebrate communities of tertiary mixtures of commonly used pesticides: 2 pyrethroids (permethrin, λ-cyhalothrin) and an organophosphate (chlorpyrifos). Application scenarios were based on environmentally relevant concentrations and stepwise increases of lethal concentrations from 10% (LC10) to 50% (LC50) based on laboratory tests on Hyalella azteca and Chironomus dilutus; repeated applications were meant to generally reflect runoff events in a multiple-grower or homeowner watershed. Pyrethroids rapidly dissipated from the water column, whereas chlorpyrifos was detectable even 6 wk after application. Twelve of 15 macroinvertebrate and 10 of 16 zooplankton taxa responded to contaminant exposures. The most sensitive taxa were the snail Radix sp., the amphipod H. azteca, the water flea Daphnia magna, and copepods. Environmentally relevant concentrations had acute effects on D. magna and H. azteca (occurring 24 h after application), whereas lag times were more pronounced in Radix sp. snails and copepods, indicating chronic sublethal responses. Greatest effects on zooplankton communities were observed in environmentally relevant concentration treatments. The results indicate that insecticide mixtures continue to impact natural systems over multiple weeks, even when no longer detectable in water and bound to particles. Combinations of indirect and direct effects caused consequences across multiple trophic levels.