Mexico City children are chronically exposed to significant concentrations of air pollutants and exhibit chronic respiratory-tract inflammation. Epidemiological, controlled human exposures, laboratory-based animal models, and in vitro/in vivo studies have shown that inflammatory, endothelial dysfunction, and endothelial damage mediators are upregulated upon exposure to particulate matter (PM). Endothelial dysfunction is a critical event in cardiovascular disease. The focus of thiswork was to investigate whether exposure to ambient air pollution including PM2.5 produces systemic inflammation and endothelial injury in healthy children. We measuredmarkers of endothelial activation, and inflammatory mediators in 52 children age 8.6±0.1 yr, residents of Mexico City (n: 28) or of Polotitlán (n: 24), a city with lowlevels of pollutants. Mexico City children had significant increases in inflammatory mediators and vasoconstrictors, including tumor necrosis factor (TNF)α, prostaglandin (PG) E2, C-reactive protein, interleukin-1β, and endothelin-1. There was a significant anti-inflammatory response, and a downregulation of vascular adhesion molecule-1, intercellular adhesion molecule-1 and -2, and selectins sE and sL. Results fromlinear regression found TNF a positively associated with 24- and 48-h cumulative levels of PM2.5, while the 7-d PM2.5 value was negatively associated with the numbers of white blood cells in peripheral blood in highly exposed children. Systemic subclinical inflammation, increased endothelin- 1, and significant downregulation of soluble adhesion molecules are seen in Mexico City children. Children chronically exposed to fine PM above the standard could be at risk of developing cardiovascular diseases, atherosclerosis, stroke, and other systemic effects later in life.