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This study was conducted to determine the aetiology of chronic renal failure (CRF) in the North Central Province of Sri Lanka. Patients (n = 183) with CRF of unknown aetiology were compared with controls (n = 200) who had no evidence of chronic renal dysfunction. Exposure to possible risk factors were determined by an interviewer-administered questionnaire. Being a farmer (P < 0.001), using pesticides (P < 0.001), drinking well water (P < 0.001), a family history of renal dysfunction (P = 0.001), use of ayurvedic treatment (P < 0.001) and a history of snake bite (P < 0.001) were risk factors for CRF of unknown aetiology. Using logistic regression analysis, a family history of chronic renal disease, taking ayurvedic treatment and history of snake bite were found to be significant predictors for CRF of unknown aetiology. There is evidence to support an environmental aetiology to CRF in Sri Lanka.