Hydrogen sulfide (H2S) is found in the central nervous system as a modulating factor, acting on hippocampus long-term potentiation, hypothalamus control of heart frequency, blood pressure and body temperature during hypoxia. In the brain, it is mainly generated from L-cysteine by cystathionine-beta-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). Therefore, aiming to understand better the actions of H2S on hypothalamus-neurohypophyseal axis, we evaluated the effects of intracerebroventricular (icv) administration of Na2S (260 nmol in 4µL of NaCl 0.9%; sulfide donor) on: a) plasma concentrations of vasopressin (AVP), oxytocin (OT), corticosterone (B), angiotensin II (ANGII), atrial natriuretic peptide (ANP), prolactin (PRL); and b) medial basal hypothalamus content of nitrates/nitrites (NOX); in euhydrated or 24-hour fluid-deprived rats (24FD).Male Wistar rats, weighing from 250 to 300g, were accommodated in 12-hour light-dark cycle, temperature of 21 ± 2°C, 5 animals per cage, chow and water ad lib, unless otherwise specified. Each one was anesthetized with ketamine (60 mg/Kg, ip) and xylazine (7.5 mg/Kg, ip), and submitted to stereotaxic surgery for cannula implantation at right lateral ventricle. For evaluation of hormone secretion and NOX content, 24FD and euhydrated animals, which were submitted to either Na2S or NaCl 0.9% icv administration, were decapitated after 5 minutes for trunk blood collection and subsequent radioimmunoassay of the hormones, or hypothalamus for quantification of NOX by chemiluminescence. Data were analyzed by two-way ANOVA, followed by Student Newman-Keuls post-hoc analysis (α=0.05). After Na2S administration (5 minutes), 24FD animals showed an 1.89-fold increase of plasma AVP level (Na2S: 6.12 ± 1.09 pg/mL vs. NaCl: 3.23 ± 0.45 pg/mL), 3.23-fold increase of plasma OT level (Na2S: 15.60 ± 3.08 pg/mL vs. NaCl: 4.82 ± 1.04 pg/mL), 1.58-fold increase of plasma B level (Na2S: 15.35 ± 1.16 µg/dL vs. NaCl: 9.69 ± 1.26 µg/dL) and 3.20-fold decrease of hypothalamus nitrate content (Na2S: 0.03 ± 0.01 nmol/µg of protein vs. NaCl: 0.09 ± 0.01 nmol/µg of protein). Plasma levels of ANGII, ANP and PRL were not changed. Na2S caused no significant changes in hormone or nitrate in euhydrated animals.We therefore suggest that H2S may be involved in the central control of AVP, OT and B secretion in water-deprivation model by interacting with nitric oxide system.