Corticotropin-releasing factor (CRF) is the principal neuropeptide involved in regulating the stress response. When centrally administered to animals it produces somatic changes analogous to those seen in both depression and anxiety. In humans, it is capable of reproducing the hormonal changes which are characteristically seen in depressed patients. A literature search using Medline, Embase Psychiatry, PsycLIT and BIDS from 1996-1997 revealed 25 studies that have examined CRF concentrations in patients with affective disorder. The methodology of these studies varies and they can be criticised, in particular, for failing to consider the stress response of the lumbar puncture. Recently, post-mortem immunocytochemical techniques have been employed to help clarify the nature of these abnormalities in depression. On balance, evidence from CSF sampling, post-mortem findings and dynamic endocrine studies suggests that both hypothalamic and extra-hypothalamic concentrations of CRF are moderately elevated in a proportion of currently antidepressant treatment, high CRF concentrations tend to normalise. The causes of increased CRF output in depression are also unknown but may involve an integration of remote vulnerability factors and recent stressors perhaps mediated through impaired function of glucocorticoid receptors. Ultimately, the careful manipulation of CRF may hold therapeutic promise for sufferers of mood disorders.