Background: Potential environmental exposures from chemical manufacturing or industrial sites have not been well studied for rural populations. The current study examines whether chemical releases from facilities monitored through the Toxics Release Inventory (TRI) program are associated with population mortality rates for both rural and urban populations. Methods: We used the TRI database, Centers for Disease Control and Prevention age-adjusted mortality data, and additional county-level covariate data to conduct a national study at (N = 3,142) of the association between amounts of on-site TRI air and water releases for the years 1988-2006 and total age-adjusted mortality rates for the years 1999-2006, after controlling for the effects of other risk variables. Results: Results of multiple linear regression analyses indicated significantly higher adjusted mortality rates associated with greater water and air releases in both rural and urban counties. The strongest associations between TRI releases and rural mortality rates were found when 8 or more prior years of TRI release data were used to study subsequent mortality. Conclusion: The results support the use of the TRI as a public reporting tool and a research tool, and demonstrate that greater amounts of air and water TRI releases are related to mortality outcomes for both rural and urban populations. (Contains 3 tables and 2 figures.)