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Summary The occurrence and distribution of nine selected antibiotics were investigated in a small Mediterranean stream (Arc River, Southern France) during the winter and the spring season. Carbamazepine and clarithromycin were the most frequently detected compounds in water. Clarithromycin was determined at high μg/L levels in river water during the winter season due to the lack of dilution by background water while clarithromycin and azithromycin were ubiquitous in sediment. These contamination levels were at one order of magnitude higher than those reported in large European rivers. It could be shown that clarithromycin can be regarded as a priority antibiotic to be monitored in river waters mainly because this chemical showed high persistence in water and underwent slow dissipation processes in sediment.