The increasing interest in regional modeling of climate change and associated decisions regarding mitigation and adaptation highlights the need to address the uncertainties that persist in projecting future climate change. Decision makers need tools and information to evaluate the implications of uncertainty for decisions that must be made before uncertainties can be reduced or resolved.Through its integrated Regional Earth System Model (iRESM) initiative, PNNL is developing a modeling framework to address regional human-environmental system interactions in response to climate change and related uncertainties. This framework is intended as a research tool for the scientific community to explore regional mitigation and adaptation decisions, constraints, and opportunities under alternate climate policy and climate change futures. The initiative is also intended to encompass research into regional decision makers' needs for information and analysis regarding mitigation and adaptation in the context of uncertainty. This research will help guide the development of iRESM's capabilities and the communication of its results. This paper presents the results of the initial research into decision support needs for the first iRESM pilot region: the US Midwest. The region is defined to include the following 14 states: Kentucky, Illinois, Indiana, Iowa, Michigan, Minnesota, Nebraska, New York, North Dakota, Ohio, Pennsylvania, South Dakota, West Virginia, and Wisconsin.The research includes interviews with regional stakeholders and a review of the published literature on mitigation and adaptation alternatives in the Midwest. The findings show that researchers as well as decision and policy makers in the Midwest are concerned about climate change impacts across a wide range of human and environmental systems and are focused on understanding the primary mitigation and adaptation opportunities and challenges within the region.The primary systems of concern for adaptation are in the areas of water resources, urban infrastructure, agriculture, recreation, ecosystems, forest management, and transportation. Potential adaptations include infrastructure modifications, technological developments, institutional changes, and ecosystem protection, enhancement, and manipulation. In the area of mitigation, the primary issues and uncertainties generally are related to: a. differential state renewable portfolio standards (RPS) b. the relative economics of technologies that reduce or eliminate GHG emissions compared to traditional technologies c. the viability of carbon storage alternatives (in both geological formations and terrestrial ecosystems).The findings demonstrate a need for better information on the interactions of socioeconomic development, climate change, natural resources, and adaptation and mitigation options. To support policy, investment, and risk management decisions, models of human and environmental systems at the regional scale such as iRESM need to be developed to better integrate climate, ecosystem, and energyecon...