We evaluated the effect of vasoactive intestinal peptide (VIP) receptor, a brain-gut peptide receptor, which is capable of exciting central neurons, on the pathogenesis of hepatic encephalopathy (HE). By means of radioligand binding assay, VIP receptors in crude synaptosomal membrane of rat brains were investigated in a rat model of HE induced by partial hepatectomy following carbon tetrachloride intoxication and in controls. A dissociation constant (Kd) was found 0.28 +/- 0.01 nmol/L and a maximal binding capacity (Bmax) 9.56 +/- 0.29 fmol/mg of protein in HE rats. Only decreased Bmax values were observed (P < 0.002) and the Kd values were statistically unchanged (P > 0.20) in HE rats as compared with in controls. The results suggest that the changes of VIP receptors in brains play a significant role in the pathogenesis of HE. The mechanism of HE induced by the alterations of VIP receptors in the brains was described.