Background: Epidemiological studies show a strong association between fine particulate matter (PM 2.5 ) air pollution and adverse pulmonary effects. While PM concentration can vary by time and location, PM toxicity has been most recently linked to both physicochemical composition and exposure scenario. To study the relevance of particle characteristics to toxicity, winter PM 2.5 samples were obtained from three geographically similar regions (Sacramento, California, USA; Jinan, Shandong, China; and Taiyuan, Shanxi, China), with typically high atmospheric PM 2.5 emissions. PM extract samples (PM CA , PM SD , and PM SX , respectively) were administered by oropharyngeal aspiration (OPA) to different groups of BALB/C mice, at equal mass concentrations [0 (water vehicle control only) or 20 µg/50 µL], on five different occasions over a two-week period, for a cumulative PM dose of 0 or 100 µg/mouse. Mice were necropsied on Days 1, 2 and 4 after the final exposure, and pulmonary effects were evaluated by bronchoalveolar lavage (BAL), histopathology, quantitative polymerase chain reaction tests, and enzyme-linked immunosorbent assays. Results: Unique differences were noted in the chemical composition for each geographic region with PM SX containing the highest concentration of sulfates (organic and inorganic). A systematic examination of the time lag effects of repeated PM exposure demonstrated unique differences. In mice administered PM SX versus the control, BAL neutrophilia, alveolitis, and bronchiolitis were observed on Days 1 and 4. By Day 4, PM SX -exposed mice also exhibited increased gene expression for multiple inflammatory cytokines/chemokines (interleukin 1 beta, tumor necrosis factor alpha, chemokine C-X-C motif ligands-3 and -5), and increased levels of monocyte chemoattractant protein-1 relative to control-, PM CA -, or PM SD -exposed mice . Conclusions: Direct comparison of the toxic effects of three geographically different PM samples on an equal mass basis demonstrate unique pathobiology with increasing lag time post-exposure. Higher sulfate levels in PM SX versus PM CA and PM SD may contribute to the greater inflammatory responses noted that progressed over time.