Abstract: HPLC determination of histamine, serotonin, dopamine, and noradrenaline in the brain tissue of rats with portocaval anastomoses (PCA) has revealed a selective increase in histamine concentration. In the posterior hypothalamus, the steady-state level of the amine metabolites showed an inverse pattern; N-tele-methylhistamine(t-MeHA), as estimated by gas chromatography-mass spectrometry, was not changed significantly by portocaval shunting, whereas 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid were more than doubled. Interestingly, the net increase in t-MeHA concentration in response to pargyline (80 mg/kg i.p.) was almost the same for PCA and sham-operated rats. This implies that the great enhancement of the histamine level in this area might be a consequence of the persistent stimulation of its synthesis and the unchanged activity of histaminergic neurons. In the rest of the brain, on the other hand, the steady-state level of t-MeHA was higher after PCA (3.8-fold), as were the levels of 5-HIAA and homovanillic acid. Surprisingly, t-MeHA remained unchanged after monoamine oxidase blockade. Of the pargyline-induced alterations in the concentrations of indoles and catechols, the most pronounced were those in the serotonin level; serotonin was elevated more than twofold in hypothalamus and more than 12-fold in the rest of the brain, with a concomitant 80% decrease in 5-HIAA. The dopamine and, to a much smaller extent, noradrenaline levels were also increased, and the levels of homovanillic acid and 3,4-dihydroxyphenylacetic acid fell below the detection limit. The study suggests that at least two different mechanisms operate in the brains of PCA rats to counteract the excessive synthesis of neuromediators, e.g., increased deposition and increased metabolism.