Calculations on the rate of entry of the neutral amino acids into the brain via the blood-brain barrier show that a considerable decrease in this rate, particularly for tryptophan and tyrosine, takes place in histidinaemia and tyrosinaemia, type II. These conditions are, however, not associated with mental retardation. It is therefore concluded that effects at the blood-brain barrier alone do not provide an adequate explanation for the aetiology of permanent brain dysfunction in hyperphenylalaninaemia.