Abstract:Chronic liver failure induced by portocaval anastomosis (PCA) in Wistar rats resulted in a dramatic increase in histamine concentration in hypothalamus and a smaller, but clearly pronounced, elevation in the rest of brain. Between 10 and 120 days following surgery, shunted rats exhibited a histamine level 2.4‐ to 13‐fold higher in hypothalamus and 1.5‐ to 2.5‐fold higher in the rest of brain as compared to their control, sham‐operated pairs. There were no significant changes in histamine concentration in the other examined tissues. The increase in brain histamine could not be attributed to the inhibition of its degradation, because activity of histamineN‐methyltransferase remained unchanged for at least 40 days. Although the activity of histidine decarboxylase also remained unchanged when measured at a saturating concentration of L‐histidine, the increase in histamine content in brain seems to be due to its enhanced synthesis brought about by increased availability of L‐histidine in the tissue, as indicated by two to four times higher concentrations of this amino a