In the lower airways, macrophages are important regulators of inflammation and indispensable in their antimicrobial activities. Thus, air pollution particles, which modulate airway macrophage host defenses may, in susceptible individuals, increase severity of inflammatory and infectious disease. In the present study, size fractionated, ultrafine (UF), fine (PM0.1-2.5), and coarse (PM2.5-10) particulate matter (PM) were collected from 2 urban sites in the Netherlands, and were compared for effects on human alveolar macrophages (AM). Inflammatory cytokine production, phagocytosis, and expression of phagocyte receptor CD11b were assessed in particle-exposed AM. Interleukin (IL)-6 levels induced by PM2.5-10 (20411 pg/mL) were > 10-fold higher than induced by PM0.1-2.5 (1781 pg/mL). Levels induced by PM0.1-2.5 were 2- to 3-fold higher than induced by UF (770 pg/mL) when cells were exposed to the same particle mass. Cytokine induction by the PM was inhibited by antibody to CD14 and required the presence of serum for optimal stimulation, implying that bacterial products or endotoxin were stimulatory moieties in both coarse and fine particulate matter. Phagocytosis of opsonized yeast was inhibited by coarse more than by fine PM, as was yeast-induced oxidative burst. Coarse particles decreased CD11b expression more than fine PM. The UF did not affect these functions. Taken together, these results suggest that PM recognition by human AM involves receptors evolved to recognize microbial cell structures, and that microbial products preferentially found in the coarse particle fraction of PM may be involved in inflammatory events and decreased pulmonary defenses associated with exposure to pollution particles.