Monoamine metabolites (5HIAA, HVA and MHPG) and cyclic nucleotides (c-AMP and c-GMP) were determined in lumbar CSF from 16 healthy controls and 36 patients hospitalized for depression. Determination of monoamine metabolites in the depressed patients was performed before and after treatment with antidepressants. The diagnosis was made according to the DSM-III (1980). The following results were obtained: 1) 5HIAA in patients with major depression was significantly lower than in controls regardless of the severity of clinical symptoms, while it was unchanged in patients with the bipolar affective disorder. It is suggested that major depression may differ biologically from the bipolar disorder. 2) The low CSF-5HIAA values in patients with major depression may not be dependent on the clinical state, but rather on a genetic trait, because they were not changed by clinical improvement or treatment with antidepressants. 3) As the initially low CSF-HVA levels in the depressed patients increased along with clinical improvement of the affective retardation, low CSF-HVA levels seem to be clinical state dependent rather than trait dependent in such patients. 4) CSF-MHPG was unchanged in the untreated depressed patients, while it decreased significantly after treatment with any of antidepressants. 5) After treatment both CSF c-AMP and c-GMP levels in completely recovered patients were significantly higher than those in control and un-improved patients. As an increase in c-AMP was found to be related to clinical improvement of depression, it seems to be state dependent in the depressed patients.