GROWA is a modular grid based empirical hydrological model that is being used to address practical water resources management related issues. It has been successfully applied in typical hydrological and hydrogeological setups of northern European basins ranging typically between meso-scale river basins of about 1000 km2 to entire States or river catchments of 100,000 km2 or more. This paper examines the applicability of this model in a typical southern European environment where the typical water resources management pattern and also the controlling hydrodynamic evolution patterns differ considerably. As such, the River Pinios basin in central Greece, which has a spatial extent of some 11.000km2, is studied. Model compilation was based on long-term average climatic and hydrological data for a reference period of 23 years (1980-2002) and validation performed against 12 river discharge gauging stations distributed in the study basin. Specific discrepancies that were denoted are attributed to the importance of secondary processes in the evolution of the studied system (e.g. overall water use, groundwater crossflows). It is concluded that prior to model recalibration efforts special attention should be given to the inclusion of such processes (water gains and losses) into the model runs. Total runoff and groundwater recharge should consequently be linked to the overall water use and secondary inputs before they are used for strategic water resources management. Overall, GROWA was successfully applied in this typical Mediterranean Basin, despite the totally different climatic, pedological, hydrological and hydrogeological conditions for which it was originally designed and tested.