Previous studies have shown that endogenous brain levels of kynurenic acid (KYNA), a glutamate receptor antagonist, are elevated in patients with schizophrenia. Here we analyse KYNA in the cerebrospinal fluid (CSF) from a large cohort, including male healthy controls (n = 49) and male patients with schizophrenia (n = 90). We found that male patients with schizophrenia had significantly higher levels of CSF KYNA compared to healthy male controls (1.45 nM +/- 0.10 vs. 1.06 nM +/- 0.06 in the control group). Furthermore, when the patients with schizophrenia were divided into subgroups we found that CSF KYNA levels were significantly elevated in drug-naive, first episode patients (1.53 nM +/- 0.19, n = 37) and in patients undergoing treatment with antipsychotic drugs (1.53 nM +/- 0.17, n = 34) compared to healthy male controls. No elevated CSF KYNA levels were detected in drug-free patients with schizophrenia, i.e. patients previously undergoing antipsychotic medications but drug-free at time of sampling (1.16 nM +/- 0.10, n = 19). Present results confirm that CSF KYNA concentration is elevated in patients with schizophrenia and are consistent with the hypothesis that KYNA contributes to the pathophysiology of the disease. (c) 2005 Elsevier B.V. All rights reserved.