The potential for regional climate change arising from adoption of policies to increase production of biofuel feedstock is explored using a regional climate model. Two simulations are performed using the same atmospheric forcing data for the period 1979–2004, one with present-day land use and monthly phenology and the other with land use specified from an agro-economic prediction of energy crop distribution and monthly phenology consistent with this land use change. In Kansas and Oklahoma, where the agro-economic model predicts 15-30% conversion to switchgrass, the regional climate model simulates locally lower temperature (especially in spring), slightly higher relative humidity in spring and slightly lower relative humidity in summer, and summer depletion of soil moisture. This shows the potential for climate impacts of biofuel policies and raises the question of whether soil water depletion may limit biomass crop productivity in agricultural areas that are responsive to the policies. We recommend the use of agronomic models to evaluate the possibility that soil moisture depletion could reduce productivity of biomass crops in this region. We conclude, therefore, that agro-economic and climate models should be used iteratively to examine an ensemble of agricultural land use and climate scenarios, thereby reducing the possibility of unforeseen consequences from rapid changes in agricultural production systems.