The pathogenesis of hepatic encephalopathy is unknown, but metabolic perturbations, including hyperammonaemia and increased brain turnover of serotonin (5-HT), have been identified. Possible alterations of 5-HT receptors in the brain have been rudimentarily studied. We therefore investigated the 5-HT1 A, 5-HT1 B and 5-HT2 A receptor density in 18-22 different regions in the brain of portacaval shunted rats by means of radioligand binding with autoradiographical evaluation. The results revealed a decreased 5-HT1 A receptor binding in seven serotonergic projection areas of the brain, and an increase in the nucleus accumbens, hypothalamus and subiculum. No changes in the raphe nuclei were observed. An increased 5-HT1 B receptor binding was seen in five brain regions: basal ganglia, olfactorial regions, hippocampus, mid brain and thalamus. However, decreased binding was seen in three regions of cortical areas and hippocampus. The 5-HT2 A receptor binding site density was essentially unaltered. These findings suggest that perturbations in the central serotonergic neurotransmission may play a functional role in chronic hepatic encephalopathy.