The potential health impact of ambient ozone and PM_2.5 concentrations modulated by climate change over the United States is investigated using combined atmospheric and health modeling. Regional air quality modeling for 2001 and 2050 was conducted using CMAQ Modeling System with meteorology from the GISS Global Climate Model, downscaled regionally using MM5, keeping boundary conditions of air pollutants, emission sources, population, activity levels, and pollution controls constant. BenMap was employed to estimate the air pollution health outcomes at the county, state, and national level for 2050 caused by the effect of meteorology on future ozone and PM_2.5 concentrations. The changes in calculated annual mean PM_2.5 concentrations show a relatively modest change with positive and negative responses (increasing PM_2.5 levels across the northeastern U.S.) although average ozone levels slightly decrease across the northern sections of the U.S., and increase across the southern tier. Results suggest that climate change driven air quality-related health effects will be adversely affected in more than 2/3 of the continental U.S. Changes in health effects induced by PM_2.5 dominate compared to those caused by ozone. PM_2.5-induced premature mortality is about 15 times higher than that due to ozone. Nationally the analysis suggests approximately 4000 additional annual premature deaths due to climate change impacts on PM_2.5 vs 300 due to climate change-induced ozone changes. However, the impacts vary spatially. Increased premature mortality due to elevated ozone concentrations will be offset by lower mortality from reductions in PM_2.5 in 11 states. Uncertainties related to different emissions projections used to simulate future climate, and the uncertainties forecasting the meteorology, are large although there are potentially important unaddressed uncertainties (e.g., downscaling, speciation, interaction, exposure, and concentration−response function of the human health studies).