Serotonergic systems were investigated in the frontal cortex of rats with thioacetamide (TAA)-induced acute hepatic encephalopathy (HE). Extracellular basal levels of 5-HT showed no difference between control and HE animals, whereas the levels of 5-HIAA were significantly increased in HE rats. Unlike basal levels, high K+-evoked 5-HT release was significantly higher in HE rats than controls. Bmax of (±)-1-(2,5-dimethoxy-4- [125I] iodophenyl)-2-aminopropane ([125I] DOI) binding, mainly labeling postsynaptic 5-HT2A receptors, was significantly decreased without any change in Kd in HE rats. These results suggest that there is no change in basal 5-HT release in the cortex of rats with TAA-induced HE despite the increase in intraneuronal 5-HT metabolism and in the size of releasable 5-HT pool, and that serotonergic neurotransmission via 5-HT2A receptor is altered in the brain area of rats with HE.