Pharmaceuticals in the environment have been subject to increasing public concern and scientific investigation over the past years. More than 100 active pharmaceutical ingredients have been detected in surface waters worldwide at the ng to microg L(-1) range. At these low levels it is commonly assumed that only chronic and/or mixture toxic effects will be discernible in aquatic ecosystems and that there are orders of magnitude between exposure and effect concentrations. Assessment of potential ecosystem risk of pharmaceuticals are recommended but rarely performed in mesocosms, so for most risk assessments the final tier to reduce extrapolation uncertainty is missing. This paper describes the fate and effects of the anthelmintic drug ivermectin for a 265-day period following treatment (nominal concentration levels of 0, 30, 100, 1000 ng L(-1) (or parts per trillion (ppt)) in fifteen 12,000 L outdoor aquatic mesocosms. Although it is established that ivermectin is highly toxic towards invertebrates, it has been believed that ivermectin does not present notable risks to aquatic systems due to the rapid dissipation of the compound and binding to the sediment. Hence, fate and exchange of ivermectin between water and sediment were evaluated in this study. The ivermectin DT(50aqueous) in water was found to be 3-5 days, but concentrations increased and appeared to be stabile in the sediment at 20-30 ng kg(-1) with no assessable DT(50sed). Acute effects (first week) following ivermectin exposure were identified and cladocerans were particularly sensitive (nom. 100 ppt). Chronic responses (<day 97) were observed for the ecosystem structure and function (nom. 30 ppt). Long-term effects (>229 days) were identified for more sediment-active organisms (e.g. Chydoriae and Ephemeroptera) (nom. 1000 ppt). This is the first study to demonstrate the potential environmental risk of ivermectin at or below the predicted environmental concentration using a standardized test methodology (mesocosm) with minimal extrapolation uncertainty.