Endemic Nephropathy (EN) is a chronic renal disease that occurs in some rural areas in Southeastern Europe. Despite numerous studies conducted to date, the etiology of this disease still remains unknown. Aristolochic acids (AA) present in Aristolochia plants are the toxins responsible for Chinese Herbs Nephropathy (CHN). Recently, strong indications have been presented, that dietary poisoning by AA is also responsible for EN and its associated urothelial cancer (UC). In the present study, we are going to investigate proteomic changes in urinary and blood specimens of model animals prone to poisoning with AA and, of patients suffering from EN and/or UC by using SELDI-TOF MS. In addition, imaging mass spectrometry (IMS), a recently developed approach for direct spatial distribution determination of tissue specific proteins will be established. The IMS will be applied for discovery and determination of specific tissue markers within the kidneys of model animals, in degenerated kidneys and/or UC of affected patients. At final, the significant proteins will be identified with LC-ESI-MS/MS and MALDI-MS. Completion of this research should provide an insight into the etiology of EN and, will lead to discovery of renal EN and associated UC biomarkers thus, enabling early diagnosis and most effective follow-up treatments.