The blood-brain uptake process for tryptophan and phenylalanine was investigated using the multiple-indicator dilution technique in 13 unanesthetized dogs with and without portacaval shunts. Tracer doses of labeled albumin (extracellular reference) and tryptophan or phenylalanine, prepared in autologous dog plasma, were injected into one carotid artery, and dorsal sagittal sinus dilution curves were obtained. Portacaval shunting was not associated with significant changes in the initial brain uptake ratio U for tryptophan or phenylalanine, despite increases in plasma phenylalanine and tyrosine. In the 13 dogs, U was not significantly correlated with the plasma levels of either the different branched-chain or aromatic amino acids or the molar ratio between these groups. These findings do not support the current hypothesis that the active transport of aromatic amino acids across the blood-brain barrier is increased after portacaval shunt. Our data suggest, instead, that the blood-brain uptake process for aromatic amino acids is linear and increases in shunted animals because their plasma levels are increased.