OBJECTIVE Our goal was to determine whether maternal smoking was associated with elevated umbilical cord erythropoietin, a marker for chronic hypoxia. METHODS Plasma erythropoietin levels were measured in umbilical cord plasma of 222 newborns. There were 48 mothers who smoked and 174 nonsmokers. RESULTS When all pregnancies were included, mean cord plasma erythropoietin levels were significantly higher in the smokers (78.0 +/- 15.3 mIU/ml) compared with the nonsmoking group (35.2 +/- 4.0 mIU/ml; p < 0.005). Regression analysis showed a significant positive correlation between the number of cigarettes smoked per day and cord plasma erythropoietin levels (r = 0.26, p < 0.0001). Smoking was associated with a significantly elevated risk (relative risk = 2.6, 95% confidence interval 1.7 to 10.9, p < 0.005) of fetal growth restriction. When pregnancies with fetal growth restriction were excluded from the analysis, the difference between the two groups remained significant (smokers 81.3 +/- 18.6, n = 38; nonsmokers 24.3 +/- 1.4, n = 164; p < 0.03). CONCLUSIONS These results illustrate that smoking during pregnancy is associated with fetal growth restriction and significantly elevated umbilical cord erythropoietin levels.