The gaseous messenger NO has repeatedly been suggested to play a role in the pathogenesis of psychoses. Following a pilot study, we investigated whether the number of nitrinergic neurons in the putamen of patients suffering from schizophrenia, bipolar disorder or major depression is altered. Post-mortem striatum sections of 15 brains from patients with either disease were examined by NADPH-diaphorase staining, which selectively labels NO synthase-positive interneurons. Quantification of these cells revealed significantly lower numbers of NO synthase-containing neurons in the putamen of schizophrenic patients. Our results suggest that striatal nitrinergic interneurons are involved in the pathophysiology of at least some forms of schizophrenia, such as e.g. catatonic schizophrenia.