The effects of chlorimipramine on the concentrations of the main metabolites of serotonin (5-HT) norepinephrine (NE), and dopamine, i.e. 5-hydroxyindoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenyl glycol (HMPG), and homovanillic acid (HVA), respectively, were studied in cerebrospinal fluid from 14 depressed patients, and related to the serotonin- and NE uptake inhibiting activity in vitro of plasma drawnfrom the patients. Chlorimipramine inhibited the uptake of both transmitter amines in all patients. During treatment, the levels of 5-HIAA and HMPG in cerebrospinal fluid (CSF) were significantly reduced. HVA levels were reduced in 6 patients and increased in 8 patients; there was no mean change. The decrease in 5-HIAA level in CSF was correlated to the uptake inhibition of 5-HT but there was no corresponding relationship between NE uptake and HMPG levels. The changes in HVA levels were also correlated to the uptake of 5-HT despite the absence of a unidirectional change of this metabolite.