SummaryObjective: The objective of this study was to determine whether women in peri-menopause are more likely to have a major mood disorder than those in pre- or postmenopause. Methods: We studied 100 women between the ages of 45 and 65 years old who were seen at four different womens health centers. Using menstrual and when available, laboratory criteria, each subject was determined to be pre-, peri- or postmenopausal. Each subject completed a Beck Depression Inventory (BDI) and provided psychiatric and medical history in a telephone interview. All patients with a BDI score greater than or equal to 10 were invited to have a psychiatric assessment, including a Structured Clinical Interview for DSM-IV Diagnoses (SCID-DSM IV). Results: The women in the perimenopausal group (n = 38) had statistically significant higher BDI scores than those women in the pre-menopausal (n = 17) and postmenopausal (n = 45) groups (p 0.0001). Of those in the perimenopausal group who scored 10 and completed the SCID and met criteria for any psychiatric diagnosis, 11 out of 22 met criteria for Major Depressive Disorder, Recurrent. Conclusions: These data suggest that perimenopause may be a associated with recurrence of pre-existing depressive illness. The findings underscore the clinical importance of screening for and treating major depressive illness in women during the menopausal years.