A disturbance of cerebral neurotransmitters and an accumulation of octopamine, a putative false neurotransmitter, have been found in patients with uremic encephalopathy who manifest disorientation, somnolence, asterixis, and coma--symptoms also seen in portal systemic encephalopathy (PSE). Altered plasma concentrations of the neutral amino acids (NAAs) and increased blood-brain NAA transport may play a role in PSE, and in the present study plasma amino acid concentrations and blood-brain barrier NAA transport were investigated in rats with acute and chronic uremia. Acute uremia was produced by unilateral nephrectomy and occlusion of the renal artery of the remaining kidney for 70 minutes; the animals were studied 24 hours later. Chronic uremia was produced by unilateral nephrectomy and 70% to 80% devascularization of the remaining kidney; these animals were studied 2 weeks later. Brain uptake was studied with the technique of Oldendorf, and blood and brain amino acids (AAs) were measured. The blood urea nitrogen (BUN) level in rats with acute uremia increased to 108 mg/dl, in rats with chronic uremic 54 mg/dl, and in sham-operated rats 22 mg/dl. In both uremic groups there was a decrease in plasma branched-chain AAs. In the brain these AA levels were normal, while levels of phenylalanine, tyrosine, and histidine were increased in uremic rats.