Evidence suggests that chemokines, proteins involved in regulation of inflammation and immune response, may have a regulatory function in pregnancy. The authors hypothesized that circulating levels of chemokines are associated with increased risk of miscarriage. Serum samples were obtained from women in the Collaborative Perinatal Project cohort who had had a miscarriage (n=439) and controls (n=373) matched by gestational age at sample collection. Concentrations of interleukin 8, epithelial cell-derived neutrophil-activating peptide (ENA)-78, macrophage inhibitory protein (MIP)-1alpha, MIP-1beta, monocyte chemotactic protein 1, and RANTES (regulated upon activation, normal T-cell-expressed, and secreted) were determined by multiplex assays, and values were standardized using the standard deviation among controls. Conditional logistic regression was used to model the relation between chemokine levels and risk of miscarriage. In multivariable analysis using all available data, the authors did not observe significant associations between any of the evaluated chemokines and miscarriage risk. In analyses using subsets of the study population based on the collection-outcome interval, elevated ENA-78 levels were associated with increased risk of miscarriage as the collection-outcome interval increased; the adjusted odds ratio was 1.25 (95% confidence interval: 1.04, 1.49) for samples collected more than 35 days prior to pregnancy outcome. The observation regarding ENA-78, which has roles in regulation of angiogenesis and leukocyte recruitment, suggests a possible role for this chemokine as an early indicator of miscarriage risk.