Epidemiological data suggest an association between smoking, respiratory infections, and impaired wound healing. Inflammation is critical in the body's defense against pathogens and in the wound-healing process. Although nicotine is used to treat some inflammatory conditions, the mechanism of this action is largely unknown. To determine how nicotine affects inflammation, rats and mice were exposed to nicotine via miniosmotic pumps, and the inflammatory response to turpentine or influenza virus was assessed. Results showed that while nicotine suppressed the migration of leukocytes to the inflammation/infection site, it increased the influenza titer in the lung. The decreased inflammation correlated with lower chemotaxis/chemokinesis of peripheral blood mononuclear cells (PBMC) toward formyl-methionyl-leucyl-phenylalanine and monocyte chemoattractant protein-1 without affecting the density of their respective receptors. However, nicotine suppressed the chemokine-induced Ca(2+) response in PBMC, indicating impaired chemokine signaling. Thus, because nicotine suppresses leukocyte migration, it might contribute to the delayed wound healing and increased incidence of respiratory infections among smokers.