• Serum cortisol levels were significantly higher after administration of 5-hydroxytryptophan (5-HTP), 200 mg orally, in unmedicated patients with affective disorders than in controls. The magnitude of the serum cortisol increase correlated positively with the Schedule for Affective Disorders and Schizophrenia—Change (SADS-C) depression syndrome ratings and correlated negatively with psychotic symptoms in 26 patients with major depression. The serum cortisol response was greater in four depressed and three manic patients who made suicide attempts than in 33 patients who were not suicidal or only had suicidal thoughts. The cortisol response was also greater in patients with bipolar depression than in those with unipolar depression and those with a first-degree relative with an affective disorder. Absence of psychotic symptoms and commission of suicidal acts were associated with an increased cortisol response to 5-HTP in the depressed patients. The cortisol response to 5-HTP in the manic patients also tended to correlate with the SADS-C manic syndrome score.