Varying levels of evidence exist for the contribution of indoor air pollution and environmental tobacco smoke as a risk factor for tuberculosis (TB). Despite a similar mechanism of action, the influence of outdoor air pollution exposure as an independent contributor to TB disease has yet to be explored. This area of inquiry is of increasing importance given the level of pollution in the rising economies of many TB-endemic nations. Los Angeles' unique physical environs and traffic patterns mirror other global megacities with a greater burden of TB therefore allowing for preliminary correlative studies. This preliminary study hypothesizes that individuals who reside proximal to elevated pollutant exposures are likely to have a greater burden of disease--as evidenced by sputum smear-positive TB. Retrospective medical records review. Medical records of non-homeless individuals (n = 196) diagnosed with culture positive TB at Los Angeles County and University of Southern California Medical Center Hospital were analyzed from January 2007 to December 2008. The study population was grouped according to acid-fast bacilli (AFB) smear-positive (n = 111) and smear-negative (n = 85) status. Air pollutant exposure was captured using measurements of ozone (O3) and particulate matter with an aerodynamic diameter of less than 2.5 (PM2.5). Individual assignment to O3 and PM2.5 exposures were based on residential proximity to the nearest US Environmental Protection Agency's monitoring station. Proximity of home residences to traffic-related pollutants occurred by measurement of distance to the nearest freeway and major non-freeway road. Single factorial models yielded a significant correlation of smear-positive status and residential exposure to PM2.5. Residential distance to freeways and major arterial roads did not yield an association. This is the first report linking ambient pollution exposure as a risk factor for TB. PM2.5 may have the potential to impact TB lung pathology as evidenced by the linkage of fine particulate matter levels and smear-positive TB.