Both short-and long-term exposure to particulate matter (PM) air pollution have been demonstrated to cause increases in cardiovascular disease, cancer, and respiratory disorders. Although the specific mechanisms by which exposure to PM cause these affects are unclear, significant evidence has accumulated to suggest that PM exposure leads to increased inflammation as the result of excessive production of reactive oxygen species (ROS) in critical cell types. In order to better understand how real-world PM exposure causes adverse health effects, there is a need to efficiently integrate metrics of PM toxicity into large scale air monitoring and health effects/epidemiology studies. Here we describe a rapid, inexpensive, method that can be employed to assess the potential of sub-mg masses of PM to generate oxidative stress in alveolar macrophage cells. Importantly, the approach is compatible with routine daily PM sampling programs such as those administered by EPA (Speciation trends network (STN), IMPROVE network, PM2.5 mass monitoring network), allowing for multiple samples to be assessed simultaneously with low volumes and brief exposure periods. We apply the method to a set of water extracts of daily PM2.5 samples (25-350 µg PM mass) collected in the Denver-Metro area. Variations in the magnitude of the ROS response observed between the samples were only partially explained by differences in mass loading, with the highest levels of ROS being observed in samples collected during the summer months. This assay provides a very useful tool that can be coupled with detailed chemical analysis and statistical models to work towards the goal of attributing PM toxicity to specific real-world chemical sources.