Effects of chronic renal failure on brain neurotransmitters (dopamine, norepinephrine, serotonin and histamine) and on monoaminergic amino acid precursors (tyrosine, phenylalanine and histidine) were investigated. To eliminate the consequences of uremia-induced restriction of food intake, rats with malnutrition (pair-fed animals) were also studied and both were compared with control rats fed ad libitum. Malnutrition of a moderate degree (food intake 84% of controls) had no effect on amino acid concentrations in plasma and brain or on neurotransmitter levels in brain. Concerning plasma amino acids in chronic renal failure a lowered tyrosine level was found resulting in a diminished tyr/phe ratio. In brain tissue, the tyr/phe ratio was found to be normal, because brain tyrosine levels in chronic renal failure were similar to controls. Histidine, which was normal in plasma at this degree of chronic renal failure, was found to be significantly enhanced in brain in uremia. Also the neurotransmitters studied were found to be elevated in brain of chronic uremia, depending on the stage of renal insufficiency.