We previously found significantly higher T3-resin uptake and nearly significantly lower total thyroxine concentrations at 38 weeks of pregnancy in women with higher postpartum depression ratings. This study further examined the relationship between thyroid status during late pregnancy and antenatal and postpartum depression scores. Thyroid measures were obtained at 32-35, 36, and 37 weeks of pregnancy in 31 women with normal range thyroid hormone levels. Subjects rated their mood at these antenatal time points and every other week between postpartum weeks 2 and 24 on the Edinburgh Postnatal Depression Scale and the Beck Depression Inventory. Mean antenatal thyroxine concentrations and free thyroxine indices correlated significantly and negatively with mean depression scores during each of three postpartum time periods (postpartum weeks 2-6, 14-18, 20-24). Women with total and free thyroxine concentrations that were, respectively, <10.1 microg/dl and <1.06 ng/dl at all three antenatal time points had significantly higher mean depression scores during all postpartum time periods. The fraction of subjects with pregravid major or minor depression history that was in the low antenatal thyroid group was significantly higher than the fraction of subjects with negative history (5/6 vs. 7/25). Women with antenatal total and free thyroxine concentrations in the lower euthyroid range may be at greater risk of developing postpartum depressive symptoms. Study of the relationships with antenatal thyroid status may provide new insights into the pathophysiology of perinatal mood disturbances.