Despite numerous studies focusing on the understanding of schizophrenia, its etiology remains unknown.Currently, available antipsychotic medications are mainly based on dopamine hypothesis, however, they exhibit partial efficacy in the treatment of the symptoms.Therefore, other neural systems have been investigated and, in this context, the glutamatergic hypothesis gained great importance.This hypothesis postulates the presence of a hypoactivity of the N-methyl-D-aspartate glutamate receptor in schizophrenia and, consequently, a deregulation of nitric oxide neurotransmission.A recent clinical trial with the administration of sodium nitroprusside, a nitric oxide donor, showed significant results in improving the symptoms of schizophrenic patients, however, no neuroimaging study investigated what are the effects of this drug on the central nervous system.The neural networks were discovered from the growing field of functional neuroimaging study and the default mode network is one of the most studied in schizophrenia.The recent functional neuroimaging studies have shown alterations in the functioning of this neural network in patients with the disease, highlighting the importance of the default mode network in the understanding of schizophrenia.In this way, the present study investigated the acute effects of sodium nitroprusside administration in the functional connectivity of the default mode network using blood oxygen level dependent (BOLD) functional magnetic resonance imaging in patients with schizophrenia and healthy volunteers.Schizophrenic patients are divided into two groups according to antipsychotic medication used: group treated without clozapine (n = 13) and group treated with clozapine (n = 13).Healthy volunteers were also divided into control group (n = 14) and control group with passive listening task (n = 5).All schizophrenic patients and healthy volunteers were subjected to a sodium nitroprusside infusion protocol simultaneously to acquisition of functional images.Our results showed increased default mode network functional connectivity with the drug infusion in patients with schizophrenia, mainly in the right hemisphere, while this same pattern was not found in healthy controls.In addition, the increase in connectivity was distinct between groups of patients because it was earlier and more extensive in the group of patients that was not in use of clozapine antipsychotic.We also note that the drug modulatory effect occurred on default mode network regions already studied and strongly implicated in the schizophrenia pathogenesis.Thus, our neurofunctional research contributed to the understanding of the sodium nitroprusside therapeutic effects on the schizophrenia symptoms.Our findings also underline the importance of sodium nitroprusside as a new adjuvant pharmacological tool in the treatment of schizophrenia.