PROBLEM: Intrauterine inflammation is a frequent and significant factor associated with the pathogenesis of preterm labor/birth (PTL/PTB). However, it remains unclear whether the intrauterine inflammatory responses activate the maternal peripheral circulation. We explored the association between PTL/PTB and the ‘activation’ of the peripheral circulatory system by determining whether CD55 mRNA expression within peripheral WBCs differed between PTL and control patients not in labor. METHOD OF STUDY: RNA was purified from white blood cells collected from pregnant women with preterm labor (n = 45), and from pregnant (n = 30) control women. CD55 gene expression was evaluated by quantitative PCR. RESULTS: The mean CD55 mRNA level within the PTL group (0.77 ± 0.03) was 1.48-fold higher than that observed (0.52 ± 0.02) within the control group (P < 0.0001); 71% of PTL patients and only 6.7% of control subjects expressed elevated CD55 mRNA. The receiver operating characteristics (with 95% CI) of CD55 as a marker for PTL were as follows: Sensitivity, 69% (53–82%); Specificity, 93% (78–99%); Positive Predictive Value, 94% (80–99%); and Negative Predictive Value, 67% (51–80%). In the patient population that delivered prematurely (before 37 weeks), 81% expressed elevated CD55 mRNA levels with a mean of 0.78 ± 0.03 and 95% CI of 0.71–0.84. The receiver operating characteristics were as follows: Sensitivity, 73% (54–88%); Specificity, 86% (71–95%); Positive Predictive Value, 81.5% (62–94%); and Negative Predictive Value, 80% (64–91%). CONCLUSION: Here we report for the first time that CD55 mRNA expression was elevated in the peripheral WBCs of subjects with preterm labor compared with control gestationally-matched pregnant woman and that elevated leukocyte CD55 may be a useful predictor of subsequent PTB.