The brain uptake of 11C-methionine was studied in 26 children with classical phenylketonuria; one adult was used as a control. Labelled methionine uptake in brain was first measured during a low phenylalanine diet and again one week later after a load of phenylalanine. Ten children aged 1 to 30 months were studied twice at intervals of several months. In children having a phenylalaninemia less than or equal to 0.3 mumoles . ml-1, a decrease in methionine brain uptake was observed with increasing age, with the largest change occurring during the first year of life. After the phenylalanine load, a mean increase in phenylalaninemia by a factor of ten was accompanied by a mean decrease in brain methionine uptake by a factor of two while blood methionine remained unchanged. Brain activity curves increased with time for children younger than one year and having phenylalaninemia less than 0.6 mumoles . ml-1. After the age of 2 most patients had a decreasing curve regardless of the blood phenylalanine level. This study indicates that 11C-methionine brain uptake may be taken as an index of blood barrier permeability to essential amino acids, and of brain maturation. The results obtained suggest that an increase in phenylalaninemia to levels greater than 0.6 mumole . ml-1 induces a modification in brain uptake of amino acids, primarily during the first two years of life.