Significant ethnic disparities exist in reproductive outcomes. A potential contributing factor may be the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and placenta during pregnancy. In the present study, levels of cortisol, ACTH and CRH were determined longitudinally from the plasma of 310 African American, Hispanic and non-Hispanic White women at 18-20, 24-26 and 30-32 weeks' gestation. During pregnancy, African American women exhibited lower levels of cortisol than non-Hispanic women and higher levels of ACTH than Hispanic women. The trajectory of CRH increase also differed by ethnicity, with African Americans exhibiting the lowest levels both early and late in pregnancy. Higher levels of cortisol at 18-20 weeks were associated with higher levels of CRH at 30-32 weeks among the African American and Hispanic women, but not among non-Hispanic women. Ethnic differences persisted when adjusting statistically for sociodemographic and biomedical factors. The findings are consistent with the possibility that ethnic disparities in adverse birth outcomes may be due, in part, to differences in HPA axis and placental function.