BACKGROUND Although pregnancy has frequently been described as a time of emotional well-being, some women experience significant antenatal depression that may require treatment with antidepressants. The purpose of this investigation was to examine the relative effects of early and late trimester exposure to fluoxetine and perinatal outcome. METHODS Obstetric and neonatal records were reviewed for 64 mother-infant pairs where there was documented use of fluoxetine at some point during pregnancy. Differences in several measures of obstetrical outcome and neonatal well-being were examined in early trimester- and late trimester-exposed infants. RESULTS No differences in birth weight and acute neonatal outcome were evident across the two groups, though there was a higher frequency of special care nursery admissions for infants with exposure to fluoxetine late in pregnancy. Special care nursery admissions could not be attributed to any specific factor. CONCLUSIONS Given the growing numbers of women who are treated with antidepressants, including fluoxetine, during pregnancy, and the strong association between depression during pregnancy and risk for postpartum depression, patients may be best advised to continue treatment with antidepressants through labor and delivery versus making any change in intensity of treatment during the acute peripartum period.