SummaryFourteen hospitalized patients with manic‐depressive psychoses received L‐5‐hydroxy‐tryptophan (L‐5‐HTP), a serotonin precursor, which has been postulated as a potent antidepressive agent. Plasma human growth hormone (HGH) and glucose levels were measured at 30 minute intervals after oral administration of 200mg of L‐5‐HTP. Plasma cortisol levels prior to L‐5‐HTP administration were also measured.1. In five manic‐depressive (bipolar) patients, aged 17 to 60, each subject studied in manic state showed an adequate HGH response of more than 5.0ng/ml (maximum levels:17.7±7.1 ng/ml Mean± S.E.M., controls, aged 27 to 41:10.5±1.6 ng/ml), while those in depressive state failed to secrete HGH adequately (maximum levels ranged 1.4‐4.8 ng/ml) (p>0.05).2. Of five determinations from three endogenous depressive (unipolar) patients, aged 30 to 51, three showed adequate responses (maximum levels ranged 2.6–16.5 ng/ml). Nine out of 10 tests from six patients with protracted depressive symptoms prolonged for 2 to 6 years, aged 45 to 65, had deficient responses of HGH (maxi mum levels: 2.1±k0.5 ng/ml Mean±S.E.M., ranged 0.1–5.6 ng/ml) (p>0.01).3. Deficiency of pituitary HGH secretion appeared to correlate neither with the score of Hamilton's Depression Scale nor with the global judgement on the severity of the illness. Increments in the blood glucose levels after L‐5‐HTP administration were only mild ones, to which HGH insensitivity may be irrelevant. Morning plasma cortisol levels in depressives, ob served as high as those in manics, also may be unrelated.4. Treatment with 300 mg of L‐5HTP daily for two weeks proved to have no favorable clinical effects on four depressive patients, who were categorized as non‐responders of HGH.Because there is evidence suggesting pituitary hormone release related to brain bio‐genic amines, the deficient HGH responses to L‐5‐HTP in depressed patients may be due to a neurochemical defect hypothesized in the manic‐depressive psychoses. The HGH responses were most distinctly diminished in the protracted depressive patients, suggesting an endocrine hypofunction which may cause the fixation of the depressive symptoms.