We assessed the oxidative potential (OP) of ambient PM_2.5 collected from many sites in the US Midwest through multiple acellular endpoints. Compared to homogeneously distributed PM_2.5, OP showed higher spatiotemporal variation. Poor correlations for the regression between mass and OP indicated a limited role of mass in determining the OP. Moreover, weak correlations among different OP endpoints justify the need for using multiple assays to determine oxidative levels of particles.