The relationship between the level of particulate air pollution (PM(10)) and the mortality and morbidity rates from respiratory and cardiovascular diseases is well established, but the biological mechanisms responsible for these associations are still unclear. The injurious effects of particulate air pollution may be either local (in the lung) or systemic. Bone-marrow release of leukocytes and platelets is an important component of the systemic inflammatory response. We have developed methods to quantify bone-marrow stimulation and showed in animals that acute exposure to ambient particles accelerates the transit of polymorphonuclear leukocytes (PMN) through the marrow whereas chronic exposure expands the size of the bone marrow pool of PMN. Human studies showed that an episode of severe air pollution stimulates the bone marrow in a manner similar to that observed in animals. In vitro and in vivo studies suggest that alveolar macrophage produce the mediators implicated in the bone marrow response to ambient particles. Cytokines produced in the lung due to deposition of ambient particles also appear in the circulation. In vitro and in vivo studies have shown that PMN recently released from the bone marrow preferentially sequester in pulmonary capillaries, are less chemotactic, and contain more damaging granular enzymes, all factors that potentate their ability to damage alveolar tissue. In animals that naturally develop atherosclerosis, deposition of ambient particles in the lung causes progression of atherosclerotic plaques with phenotypic changes in atherosclerotic plaques characteristic of lesions vulnerable to rupture. We conclude that exposure to ambient particulate matter air pollution induces a systemic inflammatory response that includes the release of inflammatory mediators into the circulation that stimulate the bone marrow to release leukocytes and platelets. We postulate that this systemic response to particulate air pollution augments lung inflammation and changes the phenotype of atherosclerotic plaques to make them more vulnerable to rupture.