Since several hours of hypoxemia in fetal animals is sufficient to cause an increase in the plasma erythropoietin level and since labor may be associated with fetal hypoxemia, this study was undertaken to determine if erythropoietin levels in cord blood were higher in fetuses subjected to labor. Two groups of term (37 to 41 weeks) singleton pregnancies were compared: (1) those delivered by elective repeat cesarean section without prior labor (n = 18) and (2) those delivered vaginally (n = 23). Erythropoietin was measured by a radioimmunoassay in which a highly purified human erythropoietin (70,000 U/mg of protein) was used and which has a sensitivity limit of 4 to 5 mU/ml. The mean cord serum erythropoietin level was higher in pregnancies with labor (46 +/- 34 mU/ml, mean +/- SD) compared to those without (26 +/- 10, p less than 0.02). There were no differences between the two groups for maternal age, gestational age, birth weight, infant sex, or Apgar scores. No association of erythropoietin with either gestational age or sex was found. In 11 pregnancies without labor, comparisons were made among simultaneously obtained samples of umbilical arterial plasma, umbilical venous plasma, and mixed cord serum. Although there were no differences between umbilical arterial and umbilical venous plasma erythropoietin levels (21.3 +/- 9.3 versus 19.0 +/- 7.8 mU/ml), mixed cord serum was inexplicably higher (24.4 +/- 9.5 mU/ml, p less than 0.01). We concluded that in uncomplicated pregnancies the duration and intensity of labor are sufficient to cause an increase in the fetal erythropoietin level at delivery.