Previous retrospective research suggests that low-level environmental lead exposure is associated with an acceleration of age-related impairment of renal function. For elucidating the long-term relationship between low-level environmental lead exposure and progression of chronic renal diseases in patients without diabetes, 121 patients who had chronic renal insufficiency, a normal body lead burden (BLB), and no history of exposure to lead were observed prospectively for 48 mo. Associations of both BLB and blood lead level (BLL) with renal function were evaluated, with reference to other covariates. The primary end point was an increase in the serum creatinine level to double the baseline value. Sixty-three patients had BLB > or =80 microg and < 600 microg (high-normal group), and 58 patients had BLB < 80 microg (low-normal group). The primary end point occurred in 17 patients. Fifteen of them had high-normal BLB, whereas two patients had low-normal BLB (hazard ratio [95% confidence interval]: 1.01 [1.00 to 1.01] for each increment of 1 microg; P = 0.002). The BLB and BLL at baseline were the most important risk factors to predict progression of renal insufficiency. Each increase of 10 microg in the BLB or 1 microg/dl in the BLL reduced the GFR by 1.3 (P = 0.002) or 4.0 ml/min (P = 0.01) during the study period. In conclusion, low-level environmental lead exposure is associated with accelerated deterioration of renal insufficiency. Even at levels far below the normal ranges, both increased BLL and BLB predict accelerated progression of chronic renal diseases.