Natural and anthropogenic land use are integral to the climate system and land use change is both a driver of, and responder to changes in climate. The potential for land use and land use change to affect global and regional climate plays a central role in the development of scenarios for greenhouse gas emissions that are used in climate model simulations. Climate models are well suited for exploring interactions with land use and land use change and a number of global and regional modeling studies have investigated past, present, and potential future climate responses induced by land use change. We assess climate responses to the land use change in the Eastern United States and Cuba during four epochs (1650, 1850, 1920, and 1992) with ensemble simulations conducted with the RegCM4 regional climate model. The 8-member ensembles for each land use epoch were driven by perturbing 1990-2002 atmospheric boundary conditions derived from the National Center for Environmental Prediction (NCEP) global reanalysis. The applied version of the model includes the Biosphere Atmosphere Transfer Scheme (BATS1e) surface physics package. We derived the land use data sets by harmonizing a previous reconstruction with updated observations and modeled potential vegetation.