Abstract The effect of streptozotocin-induced diabetes on plasma and brain neutral amino acids was studied both in normal rats and in rats with a portacaval anastomosis (PCA). In diabetic animals, plasma leucine, isoleucine, and valine were about threefold higher than control values. High plasma branched-chain amino acids were associated with decreased brain concentrations of aromatic amino acids, although the effect was most pronounced in PCA rats. The brain uptake index (BUI) of tryptophan, which is abnormally high in PCA rats, was significantly decreased in diabetic PCA rats. However, the BUI of tryptophan in diabetic PCA rats was still greater than in diabetic normal rats suggesting that some factor, besides insulin or branched-chain amino acids, affects blood-brain transport after PCA.