The serotonin and noradrenaline metabolites 5-hydroxyindole-3-acetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenyl glycol (HMPG) were determined in cerebrospinal fluid (CSF) from 18 depressed patients. HMPG levels in CSF decreased significantly when the patients were treated either with chlorimipramine or nortriptyline. 5-HIAA fell from 20.2±7.1 to 11.2±4.9 ng/ml (p<0.001) during chlorimipramine treatment, whereas it was not decreased significantly by treatment with nortriptyline. There was a significant correlation between the CSF concentration of each metabolite before and after treatment. In the seven patients who received nortriptyline the percentage fall of HMPG was more marked than that of 5-HIAA; the converse effect occurred in ten of the eleven treated with chlorimipramine. The relative effects of the two drugs on the CSF levels of 5-HIAA and HMPG were consistent with earlier studies of uptakein vitro and of turnover in animals. Chlorimipramine was a potent inhibitor of the uptake of serotonin, whereas nortriptyline had more influence on noradrenergic mechanisms.