It has been well known for at least 100 years that is an interaction between thyroid function, estrogen hormone and depressive illness. Furthermore, L-thyronine and estrogen hormones are used as adjuvant to antidepressants. We measured TT3, TT4, TSH, FT3, FT4 and E2 using immulite apparatus, in 40 depressed patients and 20 control groups. They were matched as regarding age, sex, occupation, education and socioeconomic status. Depressed group were diagnosed according to DSM-IV and were assessed by HAMD and BID. This study revealed a statistically significant difference between patients and control regarding TT3, TT4, FT3, FT4 and TSH (among premenopausal group) and E2. No significant difference was found as regard TSH between menopausal groups. There were -ve correlation between severity of depression and TT3, TT4, FT3 and E2. It was found that patients with low normal range of thyroid hormones were vulnerable to depression, whereas, menopausal women are more vulnerable, knowing that depression is buffered by estrogen effect.