To investigate the hypothesis that intrauterine growth restriction might produce a longstanding pro-inflammatory tendency, we investigated the association of low birth weight with blood levels of markers of inflammation and endothelial activation in middle-aged adults.The ARIC Study enrolled subjects aged 45–64 years sampled from four U.S. communities. An inflammation/endothelial activation score from 0 to 6 was created, one point being given for each above-median value of white blood cell count, fibrinogen, von Willebrand factor and Factor VIII, and for each below-median value of albumin and activated partial thromboplastin time.Of the 9809 individuals reporting birth weight and having all inflammation/endothelial markers and covariates, 349 (3.6%) reported low birth weight (LBW). The mean (standard deviation) score was 3.5 (1.5) for those with and 3.1 (1.6) for those without LBW (p<0.001). In robust poisson regression models adjusting for gender, ethnicity, age, study center, educational level, and current drinking and smoking status and amount, those with LBW were more likely to have a high score (≥4 points) (RR=1.16, 95% CI: 1.05–1.29).In the ARIC Study, LBW predicted greater inflammation and endothelial activation, as indicated by the higher score of blood markers, consistent with the hypothesis that early life events may result in a hyper-responsive innate immune system. Such a pro-inflammatory tendency could help explain the association of low birth weight with elements of the metabolic syndrome and ischemic heart disease.