Although various single-concentration measurements of the pharmaceutical diclofenac are available in literature, detailed information on the mass flux in the aquatic environment is often missing. Therefore, the overall load of diclofenac was obtained by recording each concentration in nine effluents of sewage treatment plants (STP) and at three river sites located in the area of the river Main (Germany) over a time period of six weeks. In STP effluents, concentrations of up to 2200 ng/L were obtained. In combination with flow rates and connected population an average specific load per capita and day of 0.28 mg (+/-0.11 mg) diclofenac reaches the receiving water course. This average specific load per capita is an expressive parameter to assess main diclofenac exposure to the aquatic environment avoiding uncertainties of estimated data commonly used in exposure assessment. Accordingly, predicted environmental concentrations (PEC) of 140 ng/L for a realistic worst case scenario and 2 to 52 ng/L based on water quality modeling were derived. Since concentrations of up to 140 ng/L were observed in surface water, the obtained PEC is in perfect agreement with measured concentrations. Hence, comparing the PEC with published predicted no effect concentrations (PNEC), chronic adverse effects in fish populations may occur.