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To evaluate the long-term mortality experience of workers exposed to arsenic, cadmium, and other substances at a copper mine and smelter in Copperhill, Tennessee studied earlier as part of an industry-wide study.Subjects were 2,422 male workers employed three or more years in the smelter or mill between 1/1/46 until the plant strike and scale-down of operations in April 1996. Vital status was determined through 2000 for 99.4% of subjects and cause of death for 91.3% of 878 deaths. Historical exposures were estimated for lead, SO2, arsenic, cadmium, dust, and cobalt. We computed standardized mortality ratios (SMRs) based on U.S. and local county rates and modeled internal relative risks (RRs).We observed overall deficits in deaths based on national and local county comparisons from all causes, all cancers and most of the cause of death categories examined. We found limited evidence of increasing mortality risks from cerebrovascular disease with increasing duration and cumulative arsenic exposure, but no evidence of an exposure-response relationship for cadmium exposure and bronchitis.Our limited evidence of an association between inhaled arsenic exposure and CVD is an exploratory finding not observed in other epidemiology studies of more highly exposed occupational populations. Possible alternative explanations include chance alone and uncontrolled confounding or effect modification by co-exposures or other factors correlated with arsenic exposure and unique to the Copperhill facility. Am. J. Ind. Med. 52:633-644, 2009. © 2009 Wiley-Liss, Inc.