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Climate change will profoundly affect socio-ecological systems, particularly those built around terrestrial ecosystems where climate is a major driver of ecological processes and ecosystem services. While socio-­ecological systems will vary in their responses to climate change, the relative sensitivities of different systems, and the mechanistic basis and consequences of these differential sensitivities, are largely unknown. At present, our ability to predict social and ecological consequences of potential climate changes in different systems is constrained by a lack of fundamental data derived from common conceptual frameworks and approaches. The LTER network is uniquely positioned to meet this critical need with a coordinated network-level approach integrating site-based and cross-site research, manipulative and natural gradient experiments, ecological and sociological approaches, and explicitly incorporating graduate student training. Accordingly, we propose a continental-scale-research program to assess how the major socio-ecological systems of the U.S. differ in their sensitivities and responses to human-caused climate change,