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The variations in serum and brain concentrations of the large neutral amino acids and the simultaneous changes in brain levels of monoamine neurotransmitters have been studied in normal and streptozotocin-diabetic rats after tryptophan loading. An impaired acute accumulation of tryptophan and serotonin in the brain of diabetic rats was observed, concomitantly with a much faster disappearance of the administered tryptophan from the bloodstream in these animals than in controls. Following the tryptophan load, transient differences in the brain levels of catecholamine neurotransmitters became also apparent between the two groups of rats in correlation with differences in the brain uptake and levels of tyrosine. In diabetic animals, the basal brain concentrations of serotonin and dopamine were normal and those of norepinephrine were increased. Since uptake of the precursors tryptophan and tyrosine from the blood is chronically reduced, it is likely that long-term adjustments of neurotransmitter metabolism occur in the diabetic brain.