SEVERAL modes of observation suggest that there may be deficient brain serotonin metabolism in the depressed patients. This serotonin hypothesis has initially been supported by a study on the brains of depressive suicides, indicative of a decrease in brainstem concentration of serotonin or its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA),’ followed by a series of reports on decreases in cerebrospinal fluid (CSF) concentrations of 5-HIAA in the depressed patients. 2 -8 Clinical attempts to treat the depressed patients with L-tryptophan and 5-hydroxytryptophan (5-HTP), the major amino acid precursors of serotonin, were also carried out and they appeared to be a relatively effective antidepressant. -11 When large doses of L-tryptophan were administered to the depressed patients, no increase in the reduced levels of CSF 5-HIAA was initially reported. This result was interpreted for evidence suggesting that some depressed patients may have a deficiency in their capacity to form serotonin from tryptophan. 12 A decrease in the accumulation of 5-HIAA in the CSF following the administration of probenecid is regarded to be good evidence of the reduced rate of brain serotonin synthesis in the depressed patients.4*51*3 However, some recent data do not agree with this hypothesis.**l4,15 On the other hand, data implicating the depletion of brain dopamine and norepinephrine have given support to the “catecholamine hypothesis” in depression. For example in the CSF studies, baseline levels of homovanillic acid (HVA), the major metabolite of dopamine, have been found to be lower in the depressed patients than in control subjects,6*15 -18 and the initial reduction of HVA was followed by a relative increase after treatment.6 Levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the major metabolite of norepinephrine, were also significantly lower in the depressed patients than in control subjects, while observed to be markedly elevated in the manic patients with a decrease to normal values during successful treatment with lithium carbonate.l6,19,*0 Exploring these two lines of “amine hypothesis” in depression, some authors, already aware of the physiological interaction between CNS serotonin and catecholamines, deem