We use Soil and Water Assessment Tool (SWAT) when driven by observations and results of climate models to evaluate hydrological quantities, including streamflow, in the Upper Mississippi River Basin (UMRB) for 1981–2003 in comparison to observed streamflow. Daily meteorological conditions used as input to SWAT are taken from (1) observations at weather stations in the basin, (2) daily meteorological conditions simulated by a collection of regional climate models (RCMs) driven by reanalysis boundary conditions, and (3) daily meteorological conditions simulated by a collection of global climate models (GCMs). Regional models used are those whose data are archived by the North American Regional Climate Change Assessment Program (NARCCAP). Results show that regional models correctly simulate the seasonal cycle of precipitation, temperature, and streamflow within the basin. Regional models also capture interannual extremes represented by the flood of 1993 and the dry conditions of 2000. The ensemble means of both the GCM-driven and RCMdriven simulations by SWAT capture both the timing and amplitude of the seasonal cycle of streamflow with neither demonstrating significant superiority at the basin level.