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Water quality is strongly related to a river’s ecosystem composition at landscape scale. Key water/sediment interfaces, referred to here as functional compartments (FCs), are the epilithic biofilm, the fine sediment at the bottom of the river and the macroporous medium or hyporheic zone, which is primarily located in the active channel where subsurface flow occurs. The function of each FC (consumption or production of organic matter and nitrate) at river reach scale was examined through modelling and calibrated within field measurements to quantify the regulation service for water quality improvement. These functions were tested on a river reach of a dominant interface function (DIF) river, the Garonne River in south-west France. It was found that: a) functions differed between the FCs as a result of biotic (organisms involved) and abiotic (hydrological and morphological) conditions, b) functions varied within each FC over time (measured, but not discussed) and c) FCs acted as transient storage zones and contributed to the development of the river’s self-purification capacity. It was concluded that in relation to the concept of river continuum, the upper reaches in the catchment were dominated by epilithic biofilm, where the main function was the production of organic matter (OM) (mean of 0.3 g·m −2 ·d −1 , range from 0.08 to −1.7), the middle course was dominated by the hyporheic zone, where the most important function was to serve as a nitrate sink (−1.25 g·m −2 ·d −1 , range from −45.6 to −0.19), and the downstream parts of the river, whose main function was the degradation of OM within the fine sediment FC (mean of -1000 g·m −2 ·d −1 , range from −960 to −1440). Hence, the morphological heterogeneity of rivers that mimic the natural mosaic of functional compartments with exchanges of water, organic matter and nutrients between compartments could contribute to enhancing their self-purification function and thus to improving water quality and system health. This study is a first step in testing the influence of the different FCs on the water quality regulation service provided by a river reach. The final objective was to be able to upscale the modelling of the different interfaces involved in a watershed’s water quality regulation service. The present study demonstrates the need to take the biophysical diversity of reaches into account in order to accurately model this regulation service. Thus the BIODIF concept of BIO-physical (biological and physical) Diversity for rivers Dominated by river-bed Interface Functions (DIF rivers) was investigated for its ability to identify the theoretical relationships between the structure and the function of regulation of a river. [ABSTRACT FROM AUTHOR]