Abstract. An integrated model is being developed to advance our understanding of the interactions between human activities, terrestrial system and water cycle, and to evaluate how system interactions will be affected by a changing climate at the regional scale. As a first step towards that goal, a global integrated assessment model, which includes a water-demand model driven by socioeconomics at regional and global scales, is coupled in a one-way fashion with a land surface hydrology-routing-water resources management model. To reconcile the scale differences between the models, a spatial and temporal disaggregation approach is developed to downscale the annual regional water demand simulations into a daily time step and subbasin representation. The model demonstrates reasonable ability to represent the historical flow regulation and water supply over the US Midwest (Missouri, Upper Mississippi, and Ohio river basins). Implications for future flow regulation, water supply, and supply deficit are investigated using climate change projections with the B1 and A2 emission scenarios, which affect both natural flow and water demand. Although natural flow is projected to increase under climate change in both the B1 and A2 scenarios, there is larger uncertainty in the changes of the regulated flow. Over the Ohio and Upper Mississippi river basins, changes in flow regulation are driven by the change in natural flow due to the limited storage capacity. However, both changes in flow and demand have effects on the Missouri River Basin summer regulated flow. Changes in demand are driven by socioeconomic factors, energy and food demands, global markets and prices with rainfed crop demand handled directly by the land surface modeling component. Even though most of the changes in supply deficit (unmet demand) and the actual supply (met demand) are driven primarily by the change in natural flow over the entire region, the integrated framework shows that supply deficit over the Missouri River Basin sees an increasing sensitivity to changes in demand in future periods. It further shows that the supply deficit is six times as sensitive as the actual supply to changes in flow and demand. A spatial analysis of the supply deficit demonstrates vulnerabilities of urban areas located along mainstream with limited storage.