Background: Prenatal antidepressant use has been associated with shorter pregnancy duration and an increased risk for preterm birth. This study measured saliva levels of estriol, a hormone that increases exponentially in the few weeks before spontaneous labor, in pregnant women with and without antidepressant treatment. Methods: Saliva estriol levels were obtained across the day at three time points during pregnancy in 77 subjects with a history of DSM-IV major depressive disorder (MDD) who were treated with antidepressants in pregnancy (Group 1), a history of DSM-IV MDD who were not treated or had limited exposure to antidepressants during pregnancy (Group 2), and a normal control group (Group 3). Results: Mean estriol levels in the second half of pregnancy were significantly higher for Group 1 (history of MDD, on meds) than Group 2 (history of MDD, off meds) or Group 3 (control). Conclusions: Prenatal antidepressant use was associated with significantly higher saliva estriol levels in the second half of pregnancy. Whether estriol reflects a causal mechanism by which women on antidepressants have shorter pregnancy duration remains to be further studied. © 2008 Society of Biological Psychiatry.