BACKGROUND Beginning in 1958, the city of Antofagasta in northern Chile was exposed to high arsenic concentrations (870 µg/L) when it switched water sources. The exposure abruptly stopped in 1970 when an arsenic-removal plant commenced operations. A unique exposure scenario like this--with an abrupt start, clear end, and large population (125,000 in 1970), all with essentially the same exposure--is rare in environmental epidemiology. Evidence of increased mortality from lung cancer, bronchiectasis, myocardial infarction, and kidney cancer has been reported among young adults who were in utero or children during the high-exposure period. OBJECTIVE We investigated other causes of mortality in Antofagasta among 30- to 49-year-old adults who were in utero or ≤ 18 years of age during the high-exposure period. METHODS We compared mortality data between Antofagasta and the rest of Chile for people 30-49 years of age during 1989-2000. We estimated expected deaths from mortality rates in all of Chile, excluding Region II where Antofagasta is located, and calculated standardized mortality ratios (SMRs). RESULTS We found evidence of increased mortality from bladder cancer [SMR = 18.1; 95% confidence interval (CI): 11.3, 27.4], laryngeal cancer (SMR = 8.1; 95% CI: 3.5, 16.0), liver cancer (SMR = 2.5; 95% CI: 1.6, 3.7), and chronic renal disease (SMR = 2.0; 95% CI: 1.5, 2.8). CONCLUSIONS Taking together our findings in the present study and previous evidence of increased mortality from other causes of death, we conclude that arsenic in Antofagasta drinking water has resulted in the greatest increases in mortality in adults < 50 years of age ever associated with early-life environmental exposure.