The association between exposure to environmental cadmium and mortality was investigated in two cohorts. The study population consisted of 275 (cohort I) and 329 (cohort II) residents (aged >or=40 years) in a cadmium-polluted area, Nagasaki Prefecture, Japan, who had participated in health surveys conducted in 1982 and 1992, respectively. The follow-up period extended from 1982 or 1992 to 2005. In the study area, the dietary cadmium intake had decreased after 1980-1983 because of the restoration of cadmium-polluted paddy fields. In cohort I, the mortality rate among those with urinary beta2-microglobulin (beta2-MG) concentration >or=1000 microg/g creatinine (cr.) was 1.41 times higher than the regional reference rate (95% confidence interval [CI] 1.07-1.83). After adjusting for age and other variables, in men, urinary N-acetyl-beta-D-glucosaminidase, and in women, serum creatinine, beta2-MG clearance, and urinary beta2-MG were significantly associated with increased mortality. However, in cohort II, urinary beta2-MG or total protein was not significantly associated with survival. These findings indicate that cadmium-induced renal dysfunction was a significant predictor of mortality, but that such an association is disappearing, probably because of the selective loss of advanced cases and reduced exposure and body burden.