The five major US Department of Energy nuclear weapons sites located in the states of Colorado, Idaho, South Carolina, Tennessee and Washington have changed functions. Environmental management of 50 years of on-site contamination is now the primary function of the sites. The cost of this cleanup is estimated at over $200 billion. A regional economic simulation model was built to estimate the economic impact of changing environmental management expenditures on the surrounding regional economies. These simulations show wide variability among the host regions in dependence on the DOE site and differences in the likelihood of producing jobs and adding to personal income from environmental management investments at the sites. Urban regions, such as Oak Ridge, are more able to convert environmental management dollars into local jobs and income than rural regions, such as the Idaho National Environmental Engineering Laboratory.