Introduction: Acutely acting tumor necrosis factor (TNF) in the circulatory system exerts a hypotensive effect via activation of nitric oxide synthase (NOS) [1]. However, long term administration of TNF triggers hypertension accompanied by decreased NOS expression [2]. Increased production of nitric oxide (NO) in the central nervous system results in a decrease of blood pressure and inhibition of NOS leads to hypertension [3]. Aim: In the present study we aimed at finding out if acutely administered TNF into the cerebral ventricles affects arterial blood pressure and heart rate and whether TNF actions are dependent on NOS activity. Methods: We carried out the study on adult male Sprague-Dawley rats. All animals were implanted with brain cannula for intracerebroventricular (ICV) infusions and arterial catheter for recording blood pressure. All surgical procedures were carried out under ketamine (100 mg/kg b.w.) and xylazine (10 mg/kg b.w.) anesthesia. Hemodynamic parameters were recorded in conscious freely moving rats at baseline and during hourly ICV infusion of saline (5 μl/hr), TNF (200 ng/5μl/hr), L-NAME (NO synthase inhibitor; 1 μg/5μl/hr), or TNF together with L-NAME in four separate groups of animals (each n=6). Mean arterial blood pressure (MABP) and heart rate (HR) were derived from raw blood pressure signal. One-way and repeated measures ANOVAs were used for statistical analysis. Results: ICV infusion of TNF caused significant increase in MABP and HR. Inhibition of NOS with ICV infusion of L-NAME resulted in significant increase of MABP without changes in HR. TNF administered together with L-NAME led to significant increase of MABP and HR. All treatments resulted in significant elevation of MABP in comparison to control animals. Coadministration of TNF and NOS inhibitor did not augment changes of hemodynamic parameters. Conclusion: Centrally administered TNF causes increase of MABP independently of brain NOS activity.