The adverse health effects resulting from ambient air pollution exposure is an increasing concern worldwide. Globally, over two-hundred epidemiologic studies report that human exposure to ambient particulate matter (PM) has a deleterious effect on cardiopulmonary mortality and morbidity, including the exacerbation of pre-existing lung disease and the development of new respiratory infections. The contribution of diesel exhaust exposure to the observed health effects is a particular concern because diesel exhaust particles (DEP) are a significant portion of fine ambient PM in many US and international cities. Previous research demonstrates that DEP exposure may enhance pulmonary vulnerability to infection by suppressing innate lung responses and enhancing allergic inflammation, but the cellular pathways involved in these processes remain unclear. The goal of the research described herein was two-fold: (1) to investigate the effects of particulate matter (PM) and diesel exhaust particle (DEP) exposure on human pulmonary inflammation; and (2) evaluate the general pathways that may be involved in DEP-induced effects. To this end, we conducted a series of in vitro experiments on human alveolar macrophages (AM) as well as a human controlled DE exposure study in order to evaluate oxidative, inflammatory mediator, and phospholipid endpoints that may be involved in DEPinduced effects. We found that DEP and ambient PM may enhance human vulnerability to lung infection by modulating alveolar macrophage (AM) oxidative and inflammatory cytokine responses to bacterial exposure. Our in vivo results demonstrated that DE exposure down-regulates TH₁ cytokine concentration and stimulates TH₂ cytokine concentrations in the bronchial fluid of exposed human volunteers, indicating that DE shifts pulmonary defense toward allergic-type mechanisms. DE exposure also decreased calcium concentration, a metal important to many immune mechanistic pathways, measured in human exhaled breath condensate. Finally, we demonstrate that in vivo DE exposure and DEP exposure in vitro alters AM phospholipid concentrations, thus potentially generating unique "fingerprints" of exposure. The results of our studies will contribute significantly to other toxicological, controlled exposure, and epidemiological studies, providing a strong data pool from which to determine the national standards that best protect public health and welfare.