The purpose of this study was to assess serotonergic function in patients with major depression or mania using sumatriptan, a novel 5-HT1D receptor agonist, as a pharmacological probe in a neuroendocrine challenge paradigm. We studied 18 drug free patients (10 with acute unipolar major depression and 8 with acute mania) who met DSM-IV criteria, and healthy controls. Subjects presented for testing after an overnight fast. After obtaining a blood sample for baseline growth hormone (GH) levels, sumatriptan (6 mg) was given subcutaneously, and further blood samples were collected at half hour intervals for 2 hours. The results showed that GH responses to sumatriptan were blunted in depressed patients but not in manics, compared to healthy controls. There were no differences in basal GH levels between the 3 groups. The results of this study provide further support for the role of serotonergic system in pathophysiology of major depression, but not in mania.