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This study investigates the applicability of selected pharmaceutical compounds (e.g. sulfamethoxazole, carbamazepine, ibuprofen) as anthropogenic indicators for the interaction of surface water and groundwater in the hyporheic zone of an alluvial stream. Differences in transport behaviour and the resulting distribution of the pharmaceuticals in the riverine groundwater were evaluated. The investigated field site in the Grand Duchy of Luxembourg, Europe is represented by low permeable sediments and confined aquifer conditions. Water samples from single-screen and multilevel observation wells installed in the riverbank at the field site were taken and analysed for selected pharmaceuticals and major ions for a period of 6 months. Surface water and groundwater levels were recorded to detect effluent and influent aquifer conditions. Nearly all pharmaceuticals that were detected in the stream were also found in the riverine groundwater. However, concentrations were significantly lower in groundwater than in surface water. A classification into mobile and sorbing/degradable pharmaceuticals based on their transport relevant properties was made and verified by the field data. Gradients with depth for some of these pharmaceuticals were documented and a more detailed understanding of the system stream/riverbank was obtained. It was demonstrated that the selected pharmaceutical compounds can be used as anthropogenic indicators at the investigated field site. However, not all compounds seem to be suitable indicators as their transport behaviour is not fully understood.