Previous work revealed the presence of LTC4 synthase in vasopressinergic neurons suggesting the involvement of leukotrienes in vasopressin secretion (1). While these mediators may activate vasopressin secretion during sepsis, they seem to inhibit during an osmotic stimulus (2, 3). Our aim was to study the effect of an inhibitor of leukotrienes synthesis (MK-886) in the hypovolemia -induced secretion of arginine vasopressin (AVP ). Male Wistar rats (250-300 g) were anesthetized with intraperitoneal (i.p.) injection of a mixture of ketamine (45 mg/kg) and xylazine (6 mg/kg) for stereotaxically implanting a stainless steel cannula into the right lateral ventricle 5-7 days before the experiment. They received an intracerebroventricular (i.c.v.) injection of 2 µl of MK-886 at doses of 1, 2 and 4 µg/kg. or vehicle (DMSO 5%) one hour before hypovolemia was induced by a intraperitoneal injection (2 ml/100 g body weight) of polyethylene glycol 4000 (PEG – 200 mg/ml) or PBS (0.01 M) was injected as control. Subsequently they were decapitated 90 minutes after the stimulus. and blood was collected for determination of hematocrit, plasma osmolality, serum sodium and plasma vasopressin levels (n= 6-14 per group). The hypothalamus (n=7-14 per group) was removed and a Western blot for the enzyme LTC4 synthase was performed. In order to assess whether PEG could induce hypovolemia without a decrease in blood pressure, four hypovolemic rats that received i.c.v injection of DMSO 5% had their mean arterial pressure evaluated throughout the experimental period. The results are reported as mean ± S.E.M. Analysis of variance (ANOVA) and a post hoc Student-Newman-Keuls (SNK) test were used to reveal statistical differences. The i.p. injection of polyethylene glycol increased the hematocrit (p>0.05), and the plasma vasopressin concentration (1.26±0.2 pg/ml vs.0.74±0.1pg/ml control) confirming the hypovolemic effect of this protocol. Nonetheless, it did not alter osmolality, serum sodium, and mean arterial pressure in any group. The central administration of MK-886 in any dose did not substantially affect the hematocrit, osmolality, or serum sodium in any of the groups. However, at higher doses (2 and 4 µg/kg) the drug was able to substantially increase even more the plasma concentration of vasopressin (3.13±0.8 pg/ml vs. 1.26±0.2 pg/ml vehicle) and (3.49±0.8 pg/ml vs.1.26±0.2 pg/ml vehicle) respectively. The groups did not show any statistical differences in hypothalamic LTC4 synthase content.The results lead us to infer that leukotrienes modulate a hypovolemia-induced vasopressin secretion in a different way than they do during sepsis.