Somatostatin-like immunoreactivity (SLI) in the brains of Eck fistula dogs, prepared as an experimental model of hepatic encephalopathy, was measured to investigate the pathogenesis of hepatic encephalopathy. The values were studied in comparison with the concentrations of amino acids where the imbalance was suggested to cause hepatic encephalopathy. SLI levels in the parietal and temporal cortex of Eck fistula dogs were 76.0 +/- 12.0 (mean +/- S.E.M., fmol/mg wet wt.) and 113.4 +/- 23.7, and those of controls were 144.0 +/- 11.8 and 186.9 +/- 19.2, respectively, the differences being statistically significant (P less than 0.005, P less than 0.05). No significant difference in gel filtration profiles of SLI in extracts from parietal and temporal cortex was observed between Eck fistula dogs and controls. Tyrosine and phenylalanine, which are suggested to be precursors of false neurotransmitters, were significantly increased in the parietal cortex of the Eck fistula dogs, and phenylalanine was significantly increased in the temporal cortex of these dogs. There was a significant negative correlation between SLI and phenylalanine concentrations in the parietal and temporal cortex (r = -0.7171, P less than 0.01). These results suggest that the reduced SLI may be one of the factors which cause the neuropsychiatric disturbances in hepatic encephalopathy.