Numerous studies show that most depressed patients show abnormal pituitary responses to challenge by intravenous injection of thyrotropin releasing hormone (TRH). Some patients show after TRH diminished thyroid stimulating hormone (TSH) release, some show unexpected growth hormone release; prolactin release may be increased or decreased. The diminished TSH release is the most widely reported finding. It cannot be accounted for by primary changes in the pituitary or thyroid glands. Interference with TRH-induced TSH release by elevated cortisol may account for some observations, but this possibility has not been studied. The present data provide additional evidence that in depression there is often a disruption of hypothalamic regulatory function.