In 1972 it was reported that in some euthyroid depressed patients the serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) was deficient. Since then, 41 reports describing 917 depressed patients have confirmed this finding. Although it is useful to report differences between mean response values of patient populations, it is necessary to identify those individuals in whom the fault occurs so that sensitivity, specificity, state-trait distribution, and clinical correlates can be determined. Present data allow some tentative conclusions: 1) the fault usually reflects a defect in central regulation of the pituitary-thyroid axis, 2) in some patients the fault may be a trait marker, and 3) it may represent a biological bridge between some depressed patients and some patients with other mental disorders.