Neuropeptide Y (NPY)-like and peptide YY (PYY)-like immunoreactivities were measured in cerebrospinal fluid (CSF) from patients with major depressive disorder or schizophrenia and from healthy volunteers without physical or mental illness. NPY-like material was significantly lower (P less than 0.001) in CSF of patients with depressive disorders than in schizophrenic patients or healthy controls. Treatment with the antidepressant, amiflamine, a selective MAO-A inhibitor, did not alter CSF peptide concentrations. In drug-free schizophrenic patients, normal NPY but reduced PYY concentrations in CSF were observed. Treatment with neuroleptics did not affect the levels of NPY or PYY in the CSF. The finding of reduced CSF concentrations of NPY in patients with major depression and of reduced PYY concentrations in schizophrenia may reflect disturbed synthesis, turnover or degradation of the peptides. These findings suggest that the reduced concentrations of NPY or PYY in the CSF may be used as trait markers of the respective illnesses.