Neurotensin (NT), a peptide which colocalizes with dopamine in some midbrain and hypothalamic neurons, has been speculated to play a role in schizophrenic illness and in the action of antipsychotic drugs. Previous work suggested a bimodal distribution of NT in patients with schizophrenia, with a subgroup having low drug-free NT concentrations which normalize with neuroleptic treatment. We studied 15 schizophrenic patients with CSF samples collected both off and on neuroleptic medication, 12 with only drug-free (DF) samples, and 10 controls. There was no significant difference in CSF NT concentrations between patients and controls, or between patients off and on medication. However, 7 patients with DFNT CSF concentrations below the patient mean showed an increase with neuroleptic treatment. Moreover, NT was significantly lower for women. Significant correlations with NT concentrations in CSF were found with deficit symptoms in patients, and with the age of the CSF sample for all subjects. There was no correlation between CSF NT concentrations and patient age, duration of illness, or levels of amine metabolites (MHPG, 5HIAA, HVA).