Patients with severe depressive illnesses of the endogenomorphic type frequently manifest several hormonal abnormalities. The best documented are the hypersecretion of cortisol, particularly in the late evening and early morning, associated with relative resistance to dexamethasone suppression; diminished or absent HGH responses to insulin-induced hypoglycemia; and diminished TSH responses to TRH. There are also reports from one laboratory of relatively diminished plasma LH concentration in postmenopausal women with primary unipolar depressive illness, a finding that awaits replication by other centers. Most of these hormonal abnormalities provide further support to the concept of hypothalamic dysfunction in certain forms of depressive illness, and are consistent with current hypotheses of abnormal brain monoamine activity in these conditions. These studies suggest that analysis of neuroendocrine responses in patients with mental illnesses may be a valuable tool for the study of possible alterations in brain function. Further advances may be expected when radioimmunoassay techniques become available for the hypothalamic releasing and inhibiting factors themselves.