The effect of intracisternal astressin, a specific and potent corticotropin-releasing factor (CRF)(1) and CRF(2) receptor antagonist on carbon tetrachloride (CCl(4))-induced acute liver injury was investigated in rats. Intracisternal astressin inhibited the elevation of serum alanine aminotransferase level induced by CCl(4). Intracisternal astressin also reduced CCl(4)-induced liver histological changes. The protective effect of central astressin on CCl(4)-induced liver damage was abolished by sympathectomy but not by hepatic branch vagotomy. These findings demonstrate that astressin acts in the central nervous system to induce hepatic cytoprotection, possibly through the sympathetic pathways in rats. These results further establish a role of endogenous CRF in the brain in hepatic pathophysiological regulation.