Previous reports suggest that massive hormonal changes that accompany the peripartum period may trigger perinatal depression. We investigated the relationship between magnitude of change and total level of estrogen and progesterone and grade of peripartal depression and depressive symptoms. One hundred and ninety two women were assessed in the 38th week of pregnancy (SDS scores), peripartum period (DSM-III-R diagnosis (n=105); SDS scores) and 6 months postpartum (EPDS; n=89) regarding diagnosis of depression, self-ratings of depressive symptoms and levels of estrogen and progesterone. The comparison of three diagnostic groups (lifetime major depressive disorder MDD (N=7), MDD at birth (N=12), healthy controls (N=70) showed that there were no differences in the magnitude of decline of estrogen and progesterone from day 1 to day 3 after birth . With respect to total levels of estrogen and progesterone, estrogen on day 3 was significantly higher [F(2,92)=6.6, p<0.05] in women with current MDD than in those with lifetime MDD or normal controls. Depression scores were significantly higher at the end of pregnancy (12.6% self-identified as depressed) than in postpartum period (5.8% day 3 p<.0004; 9.2% day 5 p<.008), whereas 13.3% of women received a DSM-III -R diagnosis for MDD 5 days postpartum. The results were in contrast to the current hypotheses of estrogen withdrawal or hypogonadal levels as an etiological factor for peripartum depression. But a limitation of the actual study is the low number of subjects with depression; therefore the current non-significant findings should be interpreted with great caution.