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The International Health Regulations (IHR) (2005) require countries to report potential public health emergencies of international concern to the World Health Organization. Given that in the U.S. federal system, disease surveillance and reporting is a state, territory, or local-level responsibility, we wanted to discern the level of familiarity at the state and local level with the international obligations for disease reporting under IHR (2005).We conducted a multisectoral survey of states, commonwealths/territories, and localities to assess basic knowledge of IHR (2005) and potential impediments to implementation. Respondents included both legal and policy experts from departments of health, agriculture, transportation, and homeland security.Our survey demonstrated that domestic knowledge of IHR (2005) and of the United States’ obligations under the regulations is not widespread, particularly in nonhealth sectors. Of the respondents who were familiar with IHR (2005), some noted legal issues as a concern for implementation, but the lack of federal guidance was perceived as a more fundamental impediment.Considerably more work needs to be done at the federal level to educate and guide state sectors for the U.S. to ensure its fulfillment of international legal obligations.