The results of an investigation of the quantitative and qualitative characteristics of Vosvozis river in Northern Greece is presented. For the purposes of this study, three gaging stations were installed along Vosvozis river, where water quantity and quality measurements were conducted for the period August 2005 to November 2006. Water discharge, temperature, pH, dissolved oxygen (DO) and electrical conductivity (EC) were measured in situ using appropriate equipment. The collected water samples were analyzed in the laboratory for the determination of nitrate, nitrite and ammonium nitrogen, total Kjeldalh nitrogen (TKN), orthophosphate (OP), total phosphorus (TP), COD, and BOD. Agricultural diffuse sources provided the major source of nitrate nitrogen loads during the wet period. During the dry period (from June to October), the major nutrient (N, P) and COD, BOD sources were point sources. The trophic status of Vosvozis river during the monitoring period was determined as eutrophic, based on Dodds classification scheme. Moreover, the SWAT model was used to simulate hydrographs and nutrient loads. SWAT was validated with the measured data. Predicted hydrographs and pollutographs were plotted against observed values and showed good agreement. The validated model was used to test eight alternative scenarios concerning different cropping management approaches. The results of these scenarios indicate that nonpoint source pollution is the prevailing type of pollution in the study area. The SWAT model was found to satisfactorily simulate processes in ephemeral river basins and is an effective tool in water resources management.