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The Total Maximum Daily Load (TMDL) program established by the United States Environmental Protection Agency (US EPA) to improve America's water quality is being applied to the Chesapeake Bay watershed to mitigate the "dead zone" problem. Agricultural activities are the major nonpoint source of nitrogen (N), contributing 44% of total N to the Bay. Best Management Practices (BMPs) are recognized as an effective way to mitigate N loss of agricultural activities. However, because of physical and economic heterogeneity in agricultural regions, targeting BMPs to areas that produce disproportionate nutrient losses has the potential to reduce the costs of achieving water quality goals. The purpose of this study is to examine the potential to reduce costs of meeting a regional water quality goal by targeting N load reductions within- and across-counties. Based on TMDL developed by the US EPA in 2010 for the Chesapeake Bay watershed, the N reduction goal is 35% for Pennsylvania by 2025. We examine the effects of targeting the required reductions within counties, across counties, and both within and across counties for the Susquehanna watershed. Using the uniform strategy to meet 35% N reduction as the baseline, results show that costs of achieving a regional 35% N reduction goal can be reduced by 13%, 31% and 36% with cross-county targeting, within-county targeting and within and across county targeting, respectively. Cost effectiveness of government subsidy programs for water quality improvement in agriculture can be increased by targeting them to areas with lower N abatement costs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)