Chronic renal failure (CRF), in the main agricultural region under reservoir based cascade irrigation in Sri Lanka has reached crisis proportion. Over 5,000 patients in the region are under treatment for CRF. The objective of this study is to establish the etiology of the CRF. Concentrations of nine heavy metals were determined in sediments, soils of reservoir peripheries, water and Nelumbo nucifera (lotus) grown in five major reservoirs that supply irrigation water. All five reservoirs carried higher levels of dissolved cadmium (Cd), iron (Fe) and lead (Pb). Dissolved Cd in reservoir water ranged from 0.03 to 0.06 mg/l. Sediment Cd concentration was 1.78-2.45 mg/kg. No arsenic (As) was detected. Cd content in lotus rhizomes was 253.82 mg/kg. The Provisional Tolerable Weekly Intake (PTWI) of Cd based on extreme exposure of rice is 8.702-15.927 microg/kg body weight (BW) for different age groups, 5-50 years. The PTWI of Cd due to extreme exposure of fish is 6.773-12.469 microg/kg BW. The PTWI on a rice staple with fish is 15.475-28.396 microg/kg BW. The mean urinary cadmium (UCd) concentration in CRF patients of age group 40-60 years was 7.58 microg Cd/g creatinine and in asymptomatic persons UCd was 11.62 microg Cd/g creatinine, indicating a chronic exposure to Cd. The possible source of Cd in reservoir sediments and water is Cd-contaminated agrochemicals. The CRF prevalent in north central Sri Lanka is a result of chronic dietary intake of Cd, supported by high natural levels of fluoride in drinking water, coupled with neglecting of routine de-silting of reservoirs for the past 20 years.