The implementation of the European Water Framework Directive requires new tools for predicting the effect of expected measures taken in the watershed on water quality at the scale of large regional river systems. In the Seine basin, four models, developed in a research context, have been chained to each other to simulate water quality and biogeochemical functioning of the hydrosystem from headwater streams to the coastal marine area. All four models are based on a similar deterministic approach and share a common description of the biogeochemical processes, allowing them to exchange information. Each model differently represents the hydro-sedimentological processes, and uses different time and space resolution, in order to tackle with the specific problematic of each sub-system. This cascade of models has been used for testing a prospective scenario of water resources management at the horizon of 2015, established by Water Authorities of the Seine-Normandy district. The simulation predicts a general improvement of water quality concerning those variables linked to point sources of pollution (ammonium, oxygen, phosphate), even if, locally, this improvement can be insufficient for meeting the expected quality standards. The predicted improvement of the quality of the Seine River downstream from Paris and its estuary is large. However, the predicted very significant drop of phosphate contamination, although beneficial for limiting the problems of coastal marine eutrophication, does not lead to a significant control of phytoplankton development in the rivers upstream from Paris. The simulation also predicts a general increase in nitrate contamination mainly linked to diffuse sources from agricultural areas.