Outdoor aquatic ditch mesocosms were treated with a range of pesticides to simulate various spray drift rates resulting from a typical crop protection program used in the cultivation of potatoes in The Netherlands. The main experimental aims of the present study were to provide information on the fate and ecological effects of drift of the pesticides into surface water and to evaluate the effectiveness of drift-reduction measures in mitigating risks. The pesticides selected and the dosage, frequency, and timing of application were based on normal agricultural practices in the potato crop. Applications of prosulfocarb, metribuzin (both herbicides), lambda-cyhalothrin (insecticide), chlorothalonil, and fluazinam (both fungicides) were made in the sequence typical of the spray calendar for potatoes. A total of 15 treatments with the various compounds were made by spray application to the water surface at 0.2%, 1%, and 5% of the recommended label rates. Chemical fate and effects on ecosystem function and structure (phytoplankton, zooplankton, chlorophyll-α, macroinvertebrates, macrophytes, breakdown of plant litter) were investigated. To interpret the observed effects, treatment concentrations were also expressed in toxic units (TU), which describe the relative toxicity of the compounds with standard toxicity test organisms (Daphnia and algae). After treatment, each compound disappeared from the water phase within 2 d, with the exception of prosulfocarb, for which 50% dissipation time (DT50) values ranged between 6 and 7 d. At the 5% treatment level, an exposure peak of 0.9 TU_algae was observed, which resulted in short-term responses of pH, oxygen, and phytoplankton. At the 5% treatment level, exposure concentrations also exceeded 0.1 TU_Daphnia, and this resulted in long-term effects on zooplankton and macroinvertebrates, some of which did not fully recover by the end of the present study. At the 1% treatment level, only slight transient effects were observed on a limited number of zooplankton and macroinvertebrate species and on pH. At the 0.2% level, no consistent treatment-related effects were observed. Most of the observed effects were consistent with the results from higher-tier and mesocosm studies with the individual compounds. Multi and repeated stress played a small role within the applied pesticide package, because of rapid dissipation of most substances and the absence of many simultaneous applications. This suggests that risk assessments based on the individual compounds would in this case have been sufficiently protective for their uses in a crop protection program.