We evaluated the potential effects of the organophosphate insecticide azinphosmethyl (AZP) in a combined microcosm and field approach. The upper regions of the Lourens River, South Africa, are free of contamination (control site), whereas the subsequent stretches flowing through a 400-ha orchard area receive transient insecticide pollution (e.g., 0.82 μg/L AZP, 344 μg/kg chlorpyrifos) following spray drift and runoff (contaminated site). Stones taken from the control site were transferred to outdoor microcosms (1.5 × 0.2 × 0.2 m), providing 12 core species and approximately 350 individuals per microcosm. Microcosms were contaminated for 1 h with AZP (control, 0.2, 1, 5, and 20 μg/L; three replicates each), and acute effects on survival were evaluated 6 d following exposure. The two strongest treatments (measured concentrations: 19.2 ± 1.0 and 4.9 ± 0.3 μg/L, respectively) resulted in a significantly (analysis of variance) reduced invertebrate density, attributed mainly to various insect taxa, such as Demoreptus sp., Castanophlebia sp., Simuliidae, and Chironomidae. In contrast, Aeshna sp., Dugesia sp., Ceratopogonidae, and Cheumatopsyche sp. were unaffected. In parallel, we conducted a quantitative macroinvertebrate survey at the control site and the contaminated site of the Lourens River after the seasonal pesticide application period. The two sites contained a similar number of species but differed considerably in their species composition and abundances. Five of the eight species that were affected by AZP in the microcosm study occurred in the field at significantly lower densities at the contaminated than at the control site or were absent at the contaminated site. All of the four species that were unaffected in the microcosm occurred at significantly higher densities at the contaminated field site. Only 3 of the 12 species reacted differently in the microcosm and the field study. We conclude that microcosm studies employing a field-relevant design could be linked successfully to field studies and our results suggest that transient pesticide contamination affects the aquatic communities of the Lourens River.